{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:14:31Z","timestamp":1768076071167,"version":"3.49.0"},"reference-count":213,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,11,25]],"date-time":"2017-11-25T00:00:00Z","timestamp":1511568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sphingolipids, long thought to be passive components of biological membranes with merely a structural role, have proved throughout the past decade to be major players in the pathogenesis of many human diseases. The study and characterization of several genetic disorders like Fabry\u2019s and Tay Sachs, where sphingolipid metabolism is disrupted, leading to a systemic array of clinical symptoms, have indeed helped elucidate and appreciate the importance of sphingolipids and their metabolites as active signaling molecules. In addition to being involved in dynamic cellular processes like apoptosis, senescence and differentiation, sphingolipids are implicated in critical physiological functions such as immune responses and pathophysiological conditions like inflammation and insulin resistance. Interestingly, the kidneys are among the most sensitive organ systems to sphingolipid alterations, rendering these molecules and the enzymes involved in their metabolism, promising therapeutic targets for numerous nephropathic complications that stand behind podocyte injury and renal failure.<\/jats:p>","DOI":"10.3390\/ijms18122528","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T11:07:08Z","timestamp":1511780828000},"page":"2528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Translational Aspects of Sphingolipid Metabolism in Renal Disorders"],"prefix":"10.3390","volume":"18","author":[{"given":"Alaa","family":"Abou Daher","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"El Jalkh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assaad","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Fornoni","sequence":"additional","affiliation":[{"name":"Department of Medicine, Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Marples","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Miller School of Medicine\/Sylvester Cancer Center, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youssef","family":"Zeidan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"},{"name":"Department of Radiation Oncology, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1152\/physrev.00020.2002","article-title":"Cell biology of the glomerular podocyte","volume":"83","author":"Pavenstadt","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3389\/fendo.2014.00127","article-title":"Podocyte pathology and nephropathy\u2014Sphingolipids in glomerular diseases","volume":"5","author":"Merscher","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/MNH.0000000000000124","article-title":"Podocyte injury and repair mechanisms","volume":"24","author":"Cellesi","year":"2015","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.kint.2016.01.012","article-title":"Podocyte injury and its consequences","volume":"89","author":"Nagata","year":"2016","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/sj.embor.7400208","article-title":"The complex life of simple sphingolipids","volume":"5","author":"Futerman","year":"2004","journal-title":"EMBO Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1016\/j.bbamem.2006.08.009","article-title":"Ceramides and other bioactive sphingolipid backbones in health and disease: Lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy","volume":"1758","author":"Zheng","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1146\/annurev.physiol.60.1.643","article-title":"Regulation of ceramide production and apoptosis","volume":"60","author":"Kolesnick","year":"1998","journal-title":"Annu. Rev. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1007\/BF02562221","article-title":"Sphingolipid metabolism in the regulation of bioactive molecules","volume":"34","author":"Luberto","year":"1999","journal-title":"Lipids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"38206","DOI":"10.1074\/jbc.M304816200","article-title":"Ceramide kinase mediates cytokine- and calcium ionophore-induced arachidonic acid release","volume":"278","author":"Pettus","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/rcm.1373","article-title":"Quantitative measurement of different ceramide species from crude cellular extracts by normal-phase high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry","volume":"18","author":"Pettus","year":"2004","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.molmed.2007.06.002","article-title":"Translational aspects of sphingolipid metabolism","volume":"13","author":"Zeidan","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.pharmthera.2006.04.004","article-title":"Bioactive sphingolipids in the modulation of the inflammatory response","volume":"112","author":"Wu","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5467","DOI":"10.1016\/j.febslet.2006.08.052","article-title":"Sphingolipids in cancer: Regulation of pathogenesis and therapy","volume":"580","author":"Ogretmen","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/j.bbamem.2006.05.027","article-title":"Sphingolipid metabolism diseases","volume":"1758","author":"Kolter","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0163-7827(97)00008-8","article-title":"The role of sphingolipids in the process of signal transduction","volume":"36","author":"Riboni","year":"1997","journal-title":"Prog. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/1097-4652(200009)184:3<285::AID-JCP2>3.0.CO;2-3","article-title":"Compartmentalization of ceramide signaling: Physical foundations and biological effects","volume":"184","author":"Kolesnick","year":"2000","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25847","DOI":"10.1074\/jbc.R200008200","article-title":"The Ceramide-centric universe of lipid-mediated cell regulation: Stress encounters of the lipid kind","volume":"277","author":"Hannun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14723","DOI":"10.1074\/jbc.M210756200","article-title":"BcR-induced apoptosis involves differential regulation of C16 and C24-ceramide formation and sphingolipid-dependent activation of the proteasome","volume":"278","author":"Kroesen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R163","DOI":"10.1016\/j.cub.2004.01.049","article-title":"Lipid metabolism: Ceramide transfer protein adds a new dimension","volume":"14","author":"Hannun","year":"2004","journal-title":"Curr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1074\/jbc.M310549200","article-title":"Rapid shortening of telomere length in response to ceramide involves the inhibition of telomere binding activity of nuclear glyceraldehyde-3-phosphate dehydrogenase","volume":"279","author":"Sundararaj","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nature02188","article-title":"Molecular machinery for non-vesicular trafficking of ceramide","volume":"426","author":"Hanada","year":"2003","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.8456305","article-title":"Programmed cell death induced by ceramide","volume":"259","author":"Obeid","year":"1993","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12275","DOI":"10.1073\/pnas.92.26.12275","article-title":"Ceramide formation during heat shock: A potential mediator of \u03b1 B-crystallin transcription","volume":"92","author":"Chang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1161\/01.RES.86.2.198","article-title":"Rapid activation of neutral sphingomyelinase by hypoxia-reoxygenation of cardiac myocytes","volume":"86","author":"Hernandez","year":"2000","journal-title":"Circ. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1016\/S0021-9258(17)35713-7","article-title":"Biosynthesis of long-chain (sphingoid) bases from serine by LM cells. Evidence for introduction of the 4-trans-double bond after de novo biosynthesis of N-acylsphinganine(s)","volume":"261","author":"Merrill","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S0022-2275(20)34349-2","article-title":"Activities of serine palmitoyltransferase (3-ketosphinganine synthase) in microsomes from different rat tissues","volume":"26","author":"Merrill","year":"1985","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9078","DOI":"10.1074\/jbc.275.12.9078","article-title":"Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis","volume":"275","author":"Perry","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6488","DOI":"10.1074\/jbc.M409290200","article-title":"CERT mediates intermembrane transfer of various molecular species of ceramides","volume":"280","author":"Kumagai","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.bbalip.2005.04.001","article-title":"Molecular mechanisms and regulation of ceramide transport","volume":"1734","author":"Perry","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4419-6741-1_1","article-title":"An overview of sphingolipid metabolism: From synthesis to breakdown","volume":"688","author":"Gault","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0300-9084(03)00047-6","article-title":"Salvage pathways in glycosphingolipid metabolism","volume":"85","author":"Tettamanti","year":"2003","journal-title":"Biochimie"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/iub.319","article-title":"Mammalian ceramide synthases","volume":"62","author":"Levy","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25001","DOI":"10.1074\/jbc.R600010200","article-title":"When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis","volume":"281","author":"Futerman","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0014-5793(97)01187-3","article-title":"Conversion of dihydroceramide to ceramide occurs at the cytosolic face of the endoplasmic reticulum","volume":"416","author":"Michel","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1139\/o03-091","article-title":"Acid and neutral sphingomyelinases: Roles and mechanisms of regulation","volume":"82","author":"Marchesini","year":"2004","journal-title":"Biochem. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3109\/01913128709048433","article-title":"Farber\u2019s disease: A fine structural study","volume":"11","author":"Abenoza","year":"1987","journal-title":"Ultrastruct. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/humu.5","article-title":"Molecular analysis of acid ceramidase deficiency in patients with Farber disease","volume":"17","author":"Bar","year":"2001","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35352","DOI":"10.1074\/jbc.M103066200","article-title":"Human acid ceramidase: Processing, glycosylation, and lysosomal targeting","volume":"276","author":"Ferlinz","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27948","DOI":"10.1074\/jbc.274.39.27948","article-title":"Purification and characterization of a membrane-bound nonlysosomal ceramidase from rat brain","volume":"274","author":"Bielawska","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1006\/bbrc.2000.3370","article-title":"Neutral\/alkaline and acid ceramidase activities are actively released by murine endothelial cells","volume":"275","author":"Romiti","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11229","DOI":"10.1074\/jbc.275.15.11229","article-title":"Molecular cloning of the full-length cDNA encoding mouse neutral ceramidase. A novel but highly conserved gene family of neutral\/alkaline ceramidases","volume":"275","author":"Tani","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21508","DOI":"10.1074\/jbc.M002522200","article-title":"Molecular cloning and characterization of a human mitochondrial ceramidase","volume":"275","author":"Roddy","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/oxfordjournals.jbchem.a003215","article-title":"Molecular cloning and characterization of a secretory neutral ceramidase of Drosophila melanogaster","volume":"132","author":"Yoshimura","year":"2002","journal-title":"J. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44012","DOI":"10.1074\/jbc.M405598200","article-title":"Molecular cloning and functional analysis of zebrafish neutral ceramidase","volume":"279","author":"Yoshimura","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"31369","DOI":"10.1074\/jbc.M003683200","article-title":"Cloning and characterization of a Saccharomyces cerevisiae alkaline ceramidase with specificity for dihydroceramide","volume":"275","author":"Mao","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6876","DOI":"10.1074\/jbc.275.10.6876","article-title":"Cloning of an alkaline ceramidase from Saccharomyces cerevisiae. An enzyme with reverse (CoA-independent) ceramide synthase activity","volume":"275","author":"Mao","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"22432","DOI":"10.1074\/jbc.272.36.22432","article-title":"Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide","volume":"272","author":"Michel","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"26249","DOI":"10.1074\/jbc.M102233200","article-title":"Purification, characterization, molecular cloning, and subcellular distribution of neutral ceramidase of rat kidney","volume":"276","author":"Mitsutake","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1074\/jbc.275.5.3462","article-title":"Purification and characterization of a neutral ceramidase from mouse liver. A single protein catalyzes the reversible reaction in which ceramide is both hydrolyzed and synthesized","volume":"275","author":"Tani","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0167-4889(89)90152-3","article-title":"Modulation of protein kinase C and diverse cell functions by sphingosine\u2014A pharmacologically interesting compound linking sphingolipids and signal transduction","volume":"1010","author":"Merrill","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26011","DOI":"10.1074\/jbc.M409081200","article-title":"Sphingosine activates protein kinase A type II by a novel cAMP-independent mechanism","volume":"280","author":"Ma","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/S1388-1981(02)00331-1","article-title":"Ceramide in apoptosis: An overview and current perspectives","volume":"1585","author":"Pettus","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/nri1650","article-title":"Sphingosine 1-phosphate and its receptors: An autocrine and paracrine network","volume":"5","author":"Rosen","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"46452","DOI":"10.1074\/jbc.M308749200","article-title":"Sphingosine kinase type 1 induces G12\/13-mediated stress fiber formation, yet promotes growth and survival independent of G protein-coupled receptors","volume":"278","author":"Olivera","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrm1103","article-title":"Sphingosine-1-phosphate: An enigmatic signalling lipid","volume":"4","author":"Spiegel","year":"2003","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/BJ20050342","article-title":"Regulation of cell survival by lipid phosphate phosphatases involves the modulation of intracellular phosphatidic acid and sphingosine 1-phosphate pools","volume":"391","author":"Long","year":"2005","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1177\/0192623314565650","article-title":"Reduced Activity of Sphingosine-1-Phosphate Lyase Induces Podocyte-related Glomerular Proteinuria, Skin Irritation, and Platelet Activation","volume":"43","author":"Schumann","year":"2015","journal-title":"Toxicol. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1172\/JCI89626","article-title":"Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency","volume":"127","author":"Lovric","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23294","DOI":"10.1074\/jbc.M201535200","article-title":"Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization","volume":"277","author":"Sugiura","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11320","DOI":"10.1074\/jbc.M309262200","article-title":"Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2","volume":"279","author":"Pettus","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature12332","article-title":"Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids","volume":"500","author":"Simanshu","year":"2013","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7427","DOI":"10.1002\/art.21668","article-title":"Sphingosine 1-phosphate\/sphingosine 1-phosphate receptor 1 signaling in rheumatoid synovium: Regulation of synovial proliferation and inflammatory gene expression","volume":"54","author":"Kitano","year":"2006","journal-title":"Arthritis Rheumatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1194\/jlr.M035683","article-title":"Characterization of eicosanoid synthesis in a genetic ablation model of ceramide kinase","volume":"54","author":"Mietla","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"44357","DOI":"10.1074\/jbc.M111.264010","article-title":"Exogenous ceramide-1-phosphate reduces lipopolysaccharide (LPS)-mediated cytokine expression","volume":"286","author":"Hankins","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrc1411","article-title":"Biologically active sphingolipids in cancer pathogenesis and treatment","volume":"4","author":"Ogretmen","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1042\/bj20021878","article-title":"Killing tumours by ceramide-induced apoptosis: A critique of available drugs","volume":"371","author":"Radin","year":"2003","journal-title":"Biochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1023\/A:1024409123726","article-title":"A phase II study of topical ceramides for cutaneous breast cancer","volume":"80","author":"Jatoi","year":"2003","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/1098-2264(2000)9999:9999<::AID-GCC1018>3.0.CO;2-E","article-title":"Human acid ceramidase is overexpressed but not mutated in prostate cancer","volume":"29","author":"Seelan","year":"2000","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0014-5793(02)02472-9","article-title":"Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes","volume":"516","author":"Raisova","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_71","first-page":"1233","article-title":"Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer","volume":"61","author":"Selzner","year":"2001","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1756-9966-31-23","article-title":"GCS overexpression is associated with multidrug resistance of human HCT-8 colon cancer cells","volume":"31","author":"Song","year":"2012","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.4161\/cbt.8.12.8374","article-title":"Co-suppression of MDR1 (multidrug resistance 1) and GCS (glucosylceramide synthase) restores sensitivity to multidrug resistance breast cancer cells by RNA interference (RNAi)","volume":"8","author":"Zhang","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_74","first-page":"701","article-title":"The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function","volume":"38","author":"Chai","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s00432-011-1016-y","article-title":"Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation","volume":"137","author":"Baran","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s12185-011-0798-7","article-title":"The effect of glucosylceramide synthase on P-glycoprotein function in K562\/AO2 leukemia drug-resistance cell line","volume":"93","author":"Zhang","year":"2011","journal-title":"Int. J. Hematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1042\/bj2800295","article-title":"Determination of the intracellular sites and topology of glucosylceramide synthesis in rat liver","volume":"280","author":"Futerman","year":"1991","journal-title":"Biochem. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1083\/jcb.117.2.259","article-title":"Glucosylceramide is synthesized at the cytosolic surface of various Golgi subfractions","volume":"117","author":"Jeckel","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/BF00731470","article-title":"Gangliosides protect human melanoma cells from ionizing radiation-induced clonogenic cell death","volume":"13","author":"Thomas","year":"1996","journal-title":"Glycoconj. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1158\/0008-5472.CAN-04-2329","article-title":"Glucosylceramide synthase blockade down-regulates P-glycoprotein and resensitizes multidrug-resistant breast cancer cells to anticancer drugs","volume":"65","author":"Gouaze","year":"2005","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ccr.2006.02.023","article-title":"Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages","volume":"9","author":"Visentin","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10664","DOI":"10.1073\/pnas.1934494100","article-title":"VEGF induces S1P1 receptors in endothelial cells: Implications for cross-talk between sphingolipid and growth factor receptors","volume":"100","author":"Igarashi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.bcp.2005.12.027","article-title":"Ceramide-1-phosphate activates cytosolic phospholipase A2\u03b1 directly and by PKC pathway","volume":"71","author":"Nakamura","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1242\/jcs.02637","article-title":"Sphingosine 1-phosphate and ceramide 1-phosphate: Expanding roles in cell signaling","volume":"118","author":"Chalfant","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1124\/mol.104.008722","article-title":"The coordination of prostaglandin E2 production by sphingosine-1-phosphate and ceramide-1-phosphate","volume":"68","author":"Pettus","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6394","DOI":"10.4049\/jimmunol.169.11.6394","article-title":"Sphingosine kinase: A point of convergence in the action of diverse neutrophil priming agents","volume":"169","author":"MacKinnon","year":"2002","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"44802","DOI":"10.1074\/jbc.M403977200","article-title":"Anaphylatoxin signaling in human neutrophils. A key role for sphingosine kinase","volume":"279","author":"Ibrahim","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1194\/jlr.M300158-JLR200","article-title":"Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages","volume":"45","author":"Kong","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0014-5793(03)00197-2","article-title":"Sphingosine-1-phosphate inhibits acid sphingomyelinase and blocks apoptosis in macrophages","volume":"539","author":"Kong","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1136\/bmj.39024.487720.68","article-title":"What have we learnt from Vioxx?","volume":"334","author":"Krumholz","year":"2007","journal-title":"BMJ"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"Matloubian","year":"2004","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1073\/pnas.95.5.2498","article-title":"Fatty acid-induced beta cell apoptosis: A link between obesity and diabetes","volume":"95","author":"Shimabukuro","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S1388-1981(02)00342-6","article-title":"Lipoapoptosis: Its mechanism and its diseases","volume":"1585","author":"Unger","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"16880","DOI":"10.1016\/S0021-9258(17)44844-7","article-title":"1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo","volume":"265","author":"Turinsky","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2337\/diabetes.53.1.25","article-title":"Ceramide content is increased in skeletal muscle from obese insulin-resistant humans","volume":"53","author":"Adams","year":"2004","journal-title":"Diabetes"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1089\/ars.2015.6562","article-title":"mTORC2 Signaling Regulates Nox4-Induced Podocyte Depletion in Diabetes","volume":"25","author":"Eid","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.abb.2003.08.020","article-title":"Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes","volume":"419","author":"Chavez","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"10297","DOI":"10.1074\/jbc.M212307200","article-title":"A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids","volume":"278","author":"Chavez","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1128\/MCB.18.9.5457","article-title":"Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide","volume":"18","author":"Summers","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.2337\/diabetes.50.11.2563","article-title":"Ceramide mediates insulin resistance by tumor necrosis factor-\u03b1 in brown adipocytes by maintaining Akt in an inactive dephosphorylated state","volume":"50","author":"Teruel","year":"2001","journal-title":"Diabetes"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.plipres.2005.11.002","article-title":"Ceramides in insulin resistance and lipotoxicity","volume":"45","author":"Summers","year":"2006","journal-title":"Prog. Lipid Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"36608","DOI":"10.1074\/jbc.M406499200","article-title":"Regulation of insulin action by ceramide: Dual mechanisms linking ceramide accumulation to the inhibition of Akt\/protein kinase B","volume":"279","author":"Stratford","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1042\/bj3540359","article-title":"Ceramide dissociates 3\u2032-phosphoinositide production from pleckstrin homology domain translocation","volume":"354","author":"Stratford","year":"2001","journal-title":"Biochem. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1038\/ki.2008.109","article-title":"Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death","volume":"73","author":"Tejada","year":"2008","journal-title":"Kidney Int."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cmet.2010.08.015","article-title":"Insulin signaling to the glomerular podocyte is critical for normal kidney function","volume":"12","author":"Welsh","year":"2010","journal-title":"Cell Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1056\/NEJMcibr1008395","article-title":"Proteinuria, the podocyte, and insulin resistance","volume":"363","author":"Fornoni","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tem.2008.09.004","article-title":"Sphingolipids: Players in the pathology of metabolic disease","volume":"20","author":"Cowart","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Fall, B., Scott, C.R., Mauer, M., Shankland, S., Pippin, J., Jefferson, J.A., Wallace, E., Warnock, D., and Najafian, B. (2016). Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168346"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Liebau, M.C., Braun, F., Hopker, K., Weitbrecht, C., Bartels, V., Muller, R.U., Brodesser, S., Saleem, M.A., Benzing, T., and Schermer, B. (2013). Dysregulated autophagy contributes to podocyte damage in Fabry\u2019s disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063506"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/hmg\/ddv291","article-title":"Lyso-Gb3 activates Notch1 in human podocytes","volume":"24","author":"Carpio","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s00428-007-0468-6","article-title":"Cellular and tissue localization of globotriaosylceramide in Fabry disease","volume":"451","author":"Askari","year":"2007","journal-title":"Virchows Arch."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1093\/ndt\/gfm848","article-title":"Nephropathy in males and females with Fabry disease: Cross-sectional description of patients before treatment with enzyme replacement therapy","volume":"23","author":"Ortiz","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/ndt\/gfs526","article-title":"Fabry nephropathy: Indications for screening and guidance for diagnosis and treatment by the European Renal Best Practice","volume":"28","author":"Terryn","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1681\/ASN.2006080816","article-title":"Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease","volume":"18","author":"Germain","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2014.74","article-title":"Therapeutic approaches to diabetic nephropathy\u2014Beyond the RAS","volume":"10","author":"Ortiz","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.bbamem.2008.09.002","article-title":"Effects of ceramide and other simple sphingolipids on membrane lateral structure","volume":"1788","author":"Goni","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1681\/ASN.2010020218","article-title":"NF-\u03baB in renal inflammation","volume":"21","author":"Sanz","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/path.2967","article-title":"Notch in the kidney: Development and disease","volume":"226","author":"Sirin","year":"2012","journal-title":"J. Pathol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nm1731","article-title":"The Notch pathway in podocytes plays a role in the development of glomerular disease","volume":"14","author":"Niranjan","year":"2008","journal-title":"Nat. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1172\/JCI43025","article-title":"Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans","volume":"120","author":"Bielesz","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/bj20021528","article-title":"Ceramide: Second messenger or modulator of membrane structure and dynamics?","volume":"369","author":"Veldman","year":"2003","journal-title":"Biochem. J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbamem.2008.07.030","article-title":"Ceramide-enriched membrane domains\u2014Structure and function","volume":"1788","author":"Zhang","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"85ra46","DOI":"10.1126\/scitranslmed.3002231","article-title":"Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis","volume":"3","author":"Fornoni","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Boini, K.M., Xia, M., Abais, J.M., Xu, M., Li, C.X., and Li, P.L. (2012). Acid sphingomyelinase gene knockout ameliorates hyperhomocysteinemic glomerular injury in mice lacking cystathionine-beta-synthase. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045020"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s001250051447","article-title":"Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria","volume":"42","author":"Meyer","year":"1999","journal-title":"Diabetologia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1046\/j.1523-1755.2001.00725.x","article-title":"Glomerular cell number in normal subjects and in type 1 diabetic patients","volume":"59","author":"Steffes","year":"2001","journal-title":"Kidney Int."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/sj.ki.5002531","article-title":"Apoptosis in the kidneys of patients with type II diabetic nephropathy","volume":"72","author":"Verzola","year":"2007","journal-title":"Kidney Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.2337\/diabetes.51.10.3083","article-title":"Podocyte number in normotensive type 1 diabetic patients with albuminuria","volume":"51","author":"White","year":"2002","journal-title":"Diabetes"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1172\/JCI119163","article-title":"Podocyte loss and progressive glomerular injury in type II diabetes","volume":"99","author":"Pagtalunan","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/BF01469685","article-title":"Plasma glycosphingolipids in diabetics and normals","volume":"53","author":"Kremer","year":"1975","journal-title":"Klin. Wochenschr."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2337\/db08-1228","article-title":"Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance","volume":"58","author":"Haus","year":"2009","journal-title":"Diabetes"},{"key":"ref_133","first-page":"CR35","article-title":"Concentrations of sphingosine and sphinganine in plasma of patients with type 2 diabetes","volume":"11","author":"Gorska","year":"2005","journal-title":"Med. Sci. Monit."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1681\/ASN.2013111213","article-title":"Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease","volume":"26","author":"Yoo","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Brunskill, E.W., and Potter, S.S. (2012). Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy. BMC Nephrol., 13.","DOI":"10.1186\/1471-2369-13-70"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1007\/s10157-014-0933-x","article-title":"Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor","volume":"18","author":"Ishizawa","year":"2014","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.2337\/db06-0330","article-title":"Altered adipose and plasma sphingolipid metabolism in obesity: A potential mechanism for cardiovascular and metabolic risk","volume":"55","author":"Samad","year":"2006","journal-title":"Diabetes"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0272-6386(04)01081-9","article-title":"Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States","volume":"44","author":"Kitiyakara","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1399-3046.2004.00181.x","article-title":"Outcomes after renal transplantation for FSGS in children","volume":"8","author":"Baum","year":"2004","journal-title":"Pediatr Transplant"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/s00467-004-1706-7","article-title":"Recurrent focal glomerulosclerosis in pediatric renal allografts: The Miami experience","volume":"20","author":"Hubsch","year":"2005","journal-title":"Pediatr. Nephrol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF00858431","article-title":"Recurrence of focal segmental glomerulosclerosis in transplanted kidneys: Analysis of incidence and risk factors in 59 allografts","volume":"4","author":"Senggutuvan","year":"1990","journal-title":"Pediatr. Nephrol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nm1696","article-title":"Modification of kidney barrier function by the urokinase receptor","volume":"14","author":"Wei","year":"2008","journal-title":"Nat. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.273.5281.1551","article-title":"Regulation of integrin function by the urokinase receptor","volume":"273","author":"Wei","year":"1996","journal-title":"Science"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrm977","article-title":"uPAR: A versatile signalling orchestrator","volume":"3","author":"Blasi","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1681\/ASN.2012030302","article-title":"Circulating suPAR in two cohorts of primary FSGS","volume":"23","author":"Wei","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.2337\/db13-0399","article-title":"Cyclodextrin protects podocytes in diabetic kidney disease","volume":"62","author":"Guzman","year":"2013","journal-title":"Diabetes"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"7962","DOI":"10.1073\/pnas.96.14.7962","article-title":"Nephrin is specifically located at the slit diaphragm of glomerular podocytes","volume":"96","author":"Ruotsalainen","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/0360-3016(94)00428-N","article-title":"Clinical radiation nephropathy","volume":"31","author":"Cassady","year":"1995","journal-title":"Int J. Radiat. Oncol. Biol. Phys."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1016\/j.ijrobp.2009.02.089","article-title":"Radiation-associated kidney injury","volume":"76","author":"Dawson","year":"2010","journal-title":"Int J. Radiat. Oncol. Biol. Phys."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.ijrobp.2009.07.1744","article-title":"Renal atrophy secondary to chemoradiotherapy of abdominal malignancies","volume":"78","author":"Yang","year":"2010","journal-title":"Int J. Radiat. Oncol. Biol. Phys."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S0270-9295(03)00093-7","article-title":"Radiation nephropathy","volume":"23","author":"Cohen","year":"2003","journal-title":"Semin. Nephrol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1667\/RR2863.1","article-title":"The association between chronic kidney disease and cardiovascular disease risk factors in atomic bomb survivors","volume":"179","author":"Sera","year":"2013","journal-title":"Radiat. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1096\/fj.201600618R","article-title":"Sphingomyelinase-like phosphodiesterase 3b mediates radiation-induced damage of renal podocytes","volume":"31","author":"Ahmad","year":"2017","journal-title":"FASEB J."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"United States Renal Data System (1998). The USRDS and its products. Am. J. Kidney Dis., 32, S20\u2013S37.","DOI":"10.1053\/ajkd.1998.v32.pm9713405"},{"key":"ref_155","first-page":"7","article-title":"Report on management of renal failure in Europe, XXII 1991","volume":"7","author":"Raine","year":"1992","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJM199809173391203","article-title":"Poor long-term survival after acute myocardial infarction among patients on long-term dialysis","volume":"339","author":"Herzog","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1681\/ASN.V71158","article-title":"Cardiovascular disease after renal transplantation","volume":"7","author":"Kasiske","year":"1996","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ahj.2004.02.004","article-title":"Homocysteine and cardiovascular disease: Biological mechanisms, observational epidemiology, and the need for randomized trials","volume":"148","author":"Splaver","year":"2004","journal-title":"Am. Heart J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1001\/jama.288.16.2015","article-title":"Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis","volume":"288","year":"2002","journal-title":"JAMA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000188545","article-title":"Reduced, free and total fractions of homocysteine and other thiol compounds in plasma from patients with renal failure","volume":"70","author":"Hultberg","year":"1995","journal-title":"Nephron"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1365-2362.1979.tb00888.x","article-title":"Sulphr containing amino acids in chronic renal failure with particular reference to homocystine and cysteine-homocysteine mixed disulphide","volume":"9","author":"Wilcken","year":"1979","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1055\/s-2000-8407","article-title":"Homocysteine and renal disease","volume":"26","author":"Robinson","year":"2000","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1172\/JCI11596","article-title":"Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways","volume":"107","author":"Werstuck","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10545-006-0106-5","article-title":"Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: An overview","volume":"29","author":"Castro","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1161\/HYPERTENSIONAHA.108.115675","article-title":"Contribution of guanine nucleotide exchange factor Vav2 to hyperhomocysteinemic glomerulosclerosis in rats","volume":"53","author":"Yi","year":"2009","journal-title":"Hypertension"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/j.1523-1755.2004.00795.x","article-title":"Activation of mesangial cell MAPK in response to homocysteine","volume":"66","author":"Ingram","year":"2004","journal-title":"Kidney Int."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/sj.ki.5001517","article-title":"Inhibition of ceramide-redox signaling pathway blocks glomerular injury in hyperhomocysteinemic rats","volume":"70","author":"Yi","year":"2006","journal-title":"Kidney Int."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"F410","DOI":"10.1152\/ajprenal.00145.2009","article-title":"Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure","volume":"297","author":"Sen","year":"2009","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1016\/j.ajpath.2011.07.019","article-title":"Acid Sphingomyelinase Gene Deficiency Ameliorates the Hyperhomocysteinemia-Induced Glomerular Injury in Mice","volume":"179","author":"Boini","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1042\/bj2910677","article-title":"The bioactive phospholipid lysophosphatidic acid is released from activated platelets","volume":"291","author":"Eichholtz","year":"1993","journal-title":"Biochem. J."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF00233943","article-title":"Sphingolipid metabolites: Members of a new class of lipid second messengers","volume":"146","author":"Spiegel","year":"1995","journal-title":"J. Membr. Biol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(95)90295-3","article-title":"Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells","volume":"80","author":"Fourcade","year":"1995","journal-title":"Cell"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/jcb.20097","article-title":"Generation and metabolism of bioactive sphingosine-1-phosphate","volume":"92","author":"Milstien","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1043-6618(03)00046-X","article-title":"Signaling and biological actions of sphingosine 1-phosphate","volume":"47","author":"Hla","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nrc1143","article-title":"The emerging role of lysophosphatidic acid in cancer","volume":"3","author":"Mills","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1042\/BST20140151","article-title":"Lysophosphatidylinositol: A novel link between ABC transporters and G-protein-coupled receptors","volume":"42","author":"Ruban","year":"2014","journal-title":"Biochem. Soc. Trans."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"20555","DOI":"10.1074\/jbc.R400013200","article-title":"Lysophospholipid G protein-coupled receptors","volume":"279","author":"Anliker","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/jcb.20108","article-title":"Thrombogenic and atherogenic activities of lysophosphatidic acid","volume":"92","author":"Siess","year":"2004","journal-title":"J. Cell Biochem."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/jcb.20129","article-title":"Mechanisms of cardioprotection by lysophospholipids","volume":"92","author":"Karliner","year":"2004","journal-title":"J. Cell Biochem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1172\/JCI200423704","article-title":"Regulation of immunity by lysosphingolipids and their G protein-coupled receptors","volume":"114","author":"Goetzl","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0014-5793(00)01510-6","article-title":"Functional characterization of human sphingosine kinase-1","volume":"473","author":"Nava","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1388-1981(02)00135-X","article-title":"Lipid phosphate phosphatases regulate signal transduction through glycerolipids and sphingolipids","volume":"1582","author":"Brindley","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/ki.2010.544","article-title":"Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes","volume":"79","author":"Awad","year":"2011","journal-title":"Kidney Int."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"F1516","DOI":"10.1152\/ajprenal.00311.2005","article-title":"Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney","volume":"290","author":"Awad","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1172\/JCI90171","article-title":"Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome","volume":"127","author":"Prasad","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1152\/physiolgenomics.00117.2003","article-title":"Microarray-based discovery of highly expressed olfactory mucosal genes: Potential roles in the various functions of the olfactory system","volume":"16","author":"Genter","year":"2003","journal-title":"Physiol. Genom."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.advenzreg.2009.10.024","article-title":"Sphingosine 1-phosphate lyase, a key regulator of sphingosine 1-phosphate signaling and function","volume":"50","author":"Serra","year":"2010","journal-title":"Adv. Enzym. Regul."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1126\/science.1113640","article-title":"Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients","volume":"309","author":"Schwab","year":"2005","journal-title":"Science"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbrc.2007.03.123","article-title":"Lack of sphingosine 1-phosphate-degrading enzymes in erythrocytes","volume":"357","author":"Ito","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1074\/jbc.272.8.5291","article-title":"Sphingosine 1-phosphate induces platelet activation through an extracellular action and shares a platelet surface receptor with lysophosphatidic acid","volume":"272","author":"Yatomi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3109\/00498251003611376","article-title":"Pharmacokinetic\/pharmacodynamic modelling of 2-acetyl-4(5)-tetrahydroxybutyl imidazole-induced peripheral lymphocyte sequestration through increasing lymphoid sphingosine 1-phosphate","volume":"40","author":"Yu","year":"2010","journal-title":"Xenobiotica"},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Billich, A., Baumruker, T., Beerli, C., Bigaud, M., Bruns, C., Calzascia, T., Isken, A., Kinzel, B., Loetscher, E., and Metzler, B. (2013). Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059630"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"8650","DOI":"10.1021\/jm101183p","article-title":"Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932)","volume":"53","author":"Bagdanoff","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Vogel, P., Donoviel, M.S., Read, R., Hansen, G.M., Hazlewood, J., Anderson, S.J., Sun, W., Swaffield, J., and Oravecz, T. (2009). Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004112"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1021\/jm500338n","article-title":"Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis","volume":"57","author":"Weiler","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1399-3046.2007.00704.x","article-title":"Contributions of the Transplant Registry: The 2006 Annual Report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)","volume":"11","author":"Smith","year":"2007","journal-title":"Pediatr. Transplant."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/ki.2008.693","article-title":"Specific podocin mutations determine age of onset of nephrotic syndrome all the way into adult life","volume":"75","author":"Hildebrandt","year":"2009","journal-title":"Kidney Int."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1053\/j.seminhematol.2010.01.011","article-title":"Rituximab: Mechanism of action","volume":"47","author":"Weiner","year":"2010","journal-title":"Semin. Hematol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1182\/blood-2005-04-1769","article-title":"Generation of biologically active linear and cyclic peptides has revealed a unique fine specificity of rituximab and its possible cross-reactivity with acid sphingomyelinase-like phosphodiesterase 3b precursor","volume":"107","author":"Perosa","year":"2006","journal-title":"Blood"},{"key":"ref_200","first-page":"29","article-title":"Rituximab: A review of dermatological applications","volume":"2","author":"Emer","year":"2009","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_201","unstructured":"Mehta, A., Beck, M., and Sunder-Plassmann, G. (2006). Enzyme replacement therapy\u2014A brief history. Fabry Disease: Perspectives from 5 Years of FOS, Oxford PharmaGenesis."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1046\/j.1523-1755.2002.00675.x","article-title":"Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy","volume":"62","author":"Thurberg","year":"2002","journal-title":"Kidney Int."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Najafian, B., Tondel, C., Svarstad, E., Sokolovkiy, A., Smith, K., and Mauer, M. (2016). One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152812"},{"key":"ref_204","first-page":"137","article-title":"Agalsidase Benefits Renal Histology in Young Patients with Fabry Disease","volume":"24","author":"Bostad","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF00731489","article-title":"Treatment of Gaucher disease with an enzyme inhibitor","volume":"13","author":"Radin","year":"1996","journal-title":"Glycoconj. J."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1517\/13543784.10.3.455","article-title":"Substrate reduction therapy for glycosphingolipid storage disorders","volume":"10","author":"Lachmann","year":"2001","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1615\/CritRevOncog.2013006060","article-title":"Gaucher disease: A comprehensive review","volume":"18","author":"Rosenbloom","year":"2013","journal-title":"Crit Rev. Oncog."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1358\/dof.2010.35.8.1505566","article-title":"ELIGLUSTAT TARTRATE: Glucosylceramide Synthase Inhibitor Treatment of Type 1 Gaucher Disease","volume":"35","author":"Shayman","year":"2010","journal-title":"Drugs Future"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1046\/j.1523-1755.2000.00864.x","article-title":"Glycosphingolipid depletion in fabry disease lymphoblasts with potent inhibitors of glucosylceramide synthase","volume":"57","author":"Abe","year":"2000","journal-title":"Kidney Int."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1172\/JCI9711","article-title":"Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation","volume":"105","author":"Abe","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/mt.2016.53","article-title":"CNS-accessible Inhibitor of Glucosylceramide Synthase for Substrate Reduction Therapy of Neuronopathic Gaucher Disease","volume":"24","author":"Marshall","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Santos, J.I., and Alves, S. (2016). Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071065"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1194\/jlr.M076745","article-title":"Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury","volume":"58","author":"Dupre","year":"2017","journal-title":"J. Lipid Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/12\/2528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:51:20Z","timestamp":1760208680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/12\/2528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,25]]},"references-count":213,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["ijms18122528"],"URL":"https:\/\/doi.org\/10.3390\/ijms18122528","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,25]]}}}