{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:04:17Z","timestamp":1767211457126,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6-2015-0042, to J.I.S."],"award-info":[{"award-number":["6-2015-0042, to J.I.S."]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1D1A1B03032457"],"award-info":[{"award-number":["2017R1D1A1B03032457"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002486","name":"Hankuk University of Foreign Studies","doi-asserted-by":"publisher","award":["to Y.H.K."],"award-info":[{"award-number":["to Y.H.K."]}],"id":[{"id":"10.13039\/501100002486","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS). This study aimed to investigate the changes in the transcriptomes of human podocytes induced by IL-4 treatment and to analyze whether these changes could be affected by simultaneous steroid treatment. Three groups of human podocytes were treated with control, IL-4, and IL-4 plus dexamethasone (DEX), respectively. We performed whole-transcriptome sequencing to identify differentially expressed genes (DEGs) between the groups. We investigated relevant biological pathways using Gene Ontology (GO) enrichment analyses. We also attempted to compare and validate the DEGs with the genes listed in PodNet, a literature-based database on mouse podocyte genes. A total of 176 genes were differentially expressed among the three groups. GO analyses showed that pathways related to cytoskeleton organization and cell signaling were significantly enriched. Among them, 24 genes were listed in PodNet, and 12 of them were previously reported to be associated with IL-4-induced changes in human podocytes. Of the 12 genes, the expression levels of BMP4, RARB, and PLCE1 were reversed when podocytes were simultaneously treated with DEX. In conclusion, this study explored changes in the transcriptome profiles of human podocytes treated with IL-4. Few genes were reported in previous studies and were previously validated in experiments with human podocytes. We speculate that IL-4 may exert pathogenic effects on the transcriptome of human podocytes, and a few genes may be involved in the pathogenesis.<\/jats:p>","DOI":"10.3390\/jcm10030496","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T03:49:48Z","timestamp":1612151388000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3932-614X","authenticated-orcid":false,"given":"Jiwon M.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Chungnam National University Hospital and College of Medicine, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Younhee","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies, Gyeonggi-do 17035, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Division of Clinical Genetics, Severance Children\u2019s Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nara","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-9587","authenticated-orcid":false,"given":"Keum Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-675X","authenticated-orcid":false,"given":"Jun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-2946","authenticated-orcid":false,"given":"Andreas","family":"Kronbichler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moin A.","family":"Saleem","sequence":"additional","affiliation":[{"name":"Children\u2019s and Renal Unit and Bristol Renal, University of Bristol, Bristol BS2 8BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beom Jin","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-1820","authenticated-orcid":false,"given":"Jae Il","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Division of Pediatric Nephrology, Severance Children\u2019s Hospital, Seoul 03722, Korea"},{"name":"Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3345\/kjp.2016.59.5.205","article-title":"Pathogenesis of minimal change nephrotic syndrome: An immunological concept","volume":"59","author":"Kim","year":"2016","journal-title":"Korean J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(03)14184-0","article-title":"Nephrotic syndrome in childhood","volume":"362","author":"Eddy","year":"2003","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrneph.2012.115","article-title":"Childhood nephrotic syndrome--current and future therapies","volume":"8","author":"Greenbaum","year":"2012","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1177\/0300060516652762","article-title":"Markers of disease and steroid responsiveness in paediatric idiopathic nephrotic syndrome: Whole-transcriptome sequencing of peripheral blood mononuclear cells","volume":"45","author":"Kang","year":"2017","journal-title":"J. Int. Med. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1159\/000350161","article-title":"The role of Th17\/IL-17 in the pathogenesis of primary nephrotic syndrome in children","volume":"37","author":"Wang","year":"2013","journal-title":"Kidney Blood Press. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.clim.2011.02.018","article-title":"Th17\/Treg imbalance in adult patients with minimal change nephrotic syndrome","volume":"139","author":"Liu","year":"2011","journal-title":"Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00467-010-1676-x","article-title":"Minimal change disease: A \"two-hit\" podocyte immune disorder?","volume":"26","author":"Shimada","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s10157-010-0330-z","article-title":"Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome","volume":"14","author":"Kanai","year":"2010","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.bbrc.2018.10.173","article-title":"Interleukin-7 stimulation inhibits nephrin activation and induces podocyte injury","volume":"507","author":"Zhai","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00011-017-1058-y","article-title":"Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13","volume":"66","author":"Ha","year":"2017","journal-title":"Inflamm Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zea, A.H., Stewart, T., Ascani, J., Tate, D.J., Finkel-Jimenez, B., Wilk, A., Reiss, K., Smoyer, W.E., and Aviles, D.H. (2016). Activation of the IL-2 Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome?. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157907"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3349\/ymj.2015.56.2.426","article-title":"Effects of interleukin-13 and montelukast on the expression of zonula occludens-1 in human podocytes","volume":"56","author":"Park","year":"2015","journal-title":"Yonsei Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1442-200X.2011.03380.x","article-title":"Elevated serum interleukin-7 level in idiopathic steroid-sensitive nephrotic syndrome","volume":"53","author":"Kanai","year":"2011","journal-title":"Pediatr. Int."},{"key":"ref_14","first-page":"298","article-title":"T helper 1 and T helper 2 cytokines in atopic children with steroid-sensitive nephrotic syndrome","volume":"9","author":"Youssef","year":"2015","journal-title":"Iran. J. Kidney Dis."},{"key":"ref_15","first-page":"83","article-title":"Type 1\/type 2 cytokine serum levels and role of interleukin-18 in children with steroid-sensitive nephrotic syndrome","volume":"6","author":"Shalaby","year":"2013","journal-title":"Arab J. Nephrol. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00467-004-1438-8","article-title":"Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome","volume":"19","author":"Cheung","year":"2004","journal-title":"Pediatr. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e81836","DOI":"10.1172\/jci.insight.81836","article-title":"B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement","volume":"2","author":"Kim","year":"2017","journal-title":"JCI Insight"},{"key":"ref_18","first-page":"S71","article-title":"Interleukin-4 receptor alpha subunit (IL-4RA) gene polymorphisms and Singapore childhood minimal change disease","volume":"32","author":"Wei","year":"2003","journal-title":"Ann. Acad. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F26","DOI":"10.1152\/ajprenal.0102.2001","article-title":"Interleukin-4 and -13 promote basolateral secretion of H(+) and cathepsin L by glomerular epithelial cells","volume":"282","author":"Aten","year":"2002","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1681\/ASN.V113413","article-title":"Interleukin-4 and interleukin-13 act on glomerular visceral epithelial cells","volume":"11","author":"Aten","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","first-page":"347","article-title":"Increased production of interleukin 4 in children with simple idiopathic nephrotic syndrome","volume":"107","author":"Kang","year":"1994","journal-title":"Chin. Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3346\/jkms.1992.7.4.343","article-title":"Studies on the role of interleukin-4 and Fc epsilon RII in the pathogenesis of minimal change nephrotic syndrome","volume":"7","author":"Cho","year":"1992","journal-title":"J. Korean Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1681\/ASN.V103529","article-title":"Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: Evidence for increased IL-13 mRNA expression in relapse","volume":"10","author":"Yap","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1681\/ASN.2006070710","article-title":"Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats","volume":"18","author":"Lai","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.cyto.2014.12.028","article-title":"Differential alteration in peripheral T-regulatory and T-effector cells with change in P-glycoprotein expression in Childhood Nephrotic Syndrome: A longitudinal study","volume":"72","author":"Prasad","year":"2015","journal-title":"Cytokine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3349\/ymj.2012.53.4.715","article-title":"The clinical characteristics of steroid responsive nephrotic syndrome of children according to the serum immunoglobulin E levels and cytokines","volume":"53","author":"Youn","year":"2012","journal-title":"Yonsei Med. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1681\/ASN.V133630","article-title":"A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression","volume":"13","author":"Saleem","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/sj.ki.5001655","article-title":"Direct effects of dexamethasone on human podocytes","volume":"70","author":"Xing","year":"2006","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/978-1-4939-3167-5_18","article-title":"Analysis of RNA-Seq Data Using TopHat and Cufflinks","volume":"1374","author":"Ghosh","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/ki.2013.64","article-title":"PodNet, a protein-protein interaction network of the podocyte","volume":"84","author":"Warsow","year":"2013","journal-title":"Kidney Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1007\/s11033-009-9761-6","article-title":"The activation of extracellular signal-regulated kinase is responsible for podocyte injury","volume":"37","author":"Liu","year":"2010","journal-title":"Mol. Biol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1111\/j.1440-1681.2008.05133.x","article-title":"Podocyte injury is suppressed by 1,25-dihydroxyvitamin D via modulation of transforming growth factor-beta 1\/bone morphogenetic protein-7 signalling in puromycin aminonucleoside nephropathy rats","volume":"36","author":"Xiao","year":"2009","journal-title":"Clin. Exp. Pharm. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1159\/000209207","article-title":"The pathogenic role of Notch activation in podocytes","volume":"111","author":"Niranjan","year":"2009","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1681\/ASN.2010080870","article-title":"The EP4 receptor for prostaglandin E2 in glomerular disease: A good receptor turned bad?","volume":"21","author":"Sparks","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1016\/j.cellsig.2008.08.007","article-title":"PGE(2) induces COX-2 expression in podocytes via the EP(4) receptor through a PKA-independent mechanism","volume":"20","author":"Faour","year":"2008","journal-title":"Cell. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1681\/ASN.2009121234","article-title":"A maladaptive role for EP4 receptors in podocytes","volume":"21","author":"Faour","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1038\/s41598-017-03237-3","article-title":"EP4 inhibition attenuates the development of diabetic and non-diabetic experimental kidney disease","volume":"7","author":"Thieme","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"F1869","DOI":"10.1152\/ajprenal.00113.2018","article-title":"Blockade of prostaglandin E2 receptor 4 ameliorates nephrotoxic serum nephritis","volume":"315","author":"Aringer","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"F1161","DOI":"10.1152\/ajprenal.00614.2011","article-title":"Both cyclin I and p35 are required for maximal survival benefit of cyclin-dependent kinase 5 in kidney podocytes","volume":"302","author":"Taniguchi","year":"2012","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"28048","DOI":"10.1074\/jbc.M513336200","article-title":"Cyclin I protects podocytes from apoptosis","volume":"281","author":"Griffin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"F112","DOI":"10.1152\/ajprenal.00171.2016","article-title":"Par3A is dispensable for the function of the glomerular filtration barrier of the kidney","volume":"311","author":"Koehler","year":"2016","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1177\/1933719111398145","article-title":"Altered nephrin and podoplanin distribution is associated with disturbed polarity protein PARD-3 and PARD-6 expressions in podocytes from preeclampsia","volume":"18","author":"Zhao","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kim, K.H., Chung, C., Kim, J.M., Lee, D., Cho, S.Y., Lee, T.H., Cho, H.J., and Yeo, M.K. (2019). Clinical significance of atypical protein kinase C (PKCiota and PKCzeta) and its relationship with yes-associated protein in lung adenocarcinoma. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5992-7"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/MNH.0b013e32832e316d","article-title":"Podocyte polarity signalling","volume":"18","author":"Simons","year":"2009","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1681\/ASN.2008080871","article-title":"Loss of podocyte aPKClambda\/iota causes polarity defects and nephrotic syndrome","volume":"20","author":"Huber","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/s41467-019-09720-x","article-title":"KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a","volume":"10","author":"Song","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.3892\/mmr.2017.7708","article-title":"WWC1 promotes podocyte survival via stabilizing slit diaphragm protein dendrin","volume":"16","author":"Lin","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1681\/ASN.2007080916","article-title":"KIBRA modulates directional migration of podocytes","volume":"19","author":"Duning","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21137","DOI":"10.1074\/jbc.M117.819029","article-title":"The Hippo pathway regulator KIBRA promotes podocyte injury by inhibiting YAP signaling and disrupting actin cytoskeletal dynamics","volume":"292","author":"Meliambro","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17383","DOI":"10.1074\/jbc.RA119.009589","article-title":"Intrinsic disorder and amino acid specificity modulate binding of the WW2 domain in kidney and brain protein (KIBRA) to synaptopodin","volume":"294","author":"Kwok","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0002-9440(10)63354-8","article-title":"Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin","volume":"165","author":"Lehtonen","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Beaudreuil, S., Zhang, X., Herr, F., Harper, F., Candelier, J.J., Fan, Y., Yeter, H., Dudreuilh, C., Lecru, L., and Vazquez, A. (2019). Circulating CASK is associated with recurrent focal segmental glomerulosclerosis after transplantation. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219353"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1002\/1873-3468.13081","article-title":"The tale of two talins-two isoforms to fine-tune integrin signalling","volume":"592","author":"Gough","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_55","first-page":"4148","article-title":"Talin regulates integrin beta1-dependent and -independent cell functions in ureteric bud development","volume":"144","author":"Mathew","year":"2017","journal-title":"Development"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1172\/JCI46458","article-title":"Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis","volume":"121","author":"Akilesh","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1172\/JCI99507","article-title":"CaMK4 compromises podocyte function in autoimmune and nonautoimmune kidney disease","volume":"128","author":"Maeda","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"23368","DOI":"10.1074\/jbc.M113.460394","article-title":"Calmodulin-dependent protein kinase II\/cAMP response element-binding protein\/Wnt\/beta-catenin signaling cascade regulates angiotensin II-induced podocyte injury and albuminuria","volume":"288","author":"Jiang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1038\/ng1918","article-title":"Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible","volume":"38","author":"Hinkes","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/ndt\/gfm759","article-title":"Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS)","volume":"23","author":"Gbadegesin","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12027","DOI":"10.1074\/jbc.M112.345421","article-title":"Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors","volume":"287","author":"Khurana","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1124\/jpet.118.249375","article-title":"Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptor beta2 Agonist","volume":"367","author":"Trasino","year":"2018","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1681\/ASN.2006090983","article-title":"Bmp in podocytes is essential for normal glomerular capillary formation","volume":"19","author":"Ueda","year":"2008","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/3\/496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:18:01Z","timestamp":1760159881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/3\/496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["jcm10030496"],"URL":"https:\/\/doi.org\/10.3390\/jcm10030496","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2021,2,1]]}}}