{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:44:50Z","timestamp":1787316290887,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"PCT","doi-asserted-by":"publisher","award":["R21AR077260"],"award-info":[{"award-number":["R21AR077260"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"PCT","doi-asserted-by":"publisher","award":["R01EY025528"],"award-info":[{"award-number":["R01EY025528"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"SR.","doi-asserted-by":"publisher","award":["R21AR077260"],"award-info":[{"award-number":["R21AR077260"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"SR.","doi-asserted-by":"publisher","award":["R01EY025528"],"award-info":[{"award-number":["R01EY025528"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysyl oxidases are multifunctional proteins derived from five lysyl oxidase paralogues (LOX) and lysyl oxidase-like 1 through lysyl oxidase-like 4 (LOXL1\u2013LOXL4). All participate in the biosynthesis of and maturation of connective tissues by catalyzing the oxidative deamination of lysine residues in collagens and elastin, which ultimately results in the development of cross-links required to function. In addition, the five LOX genes have been linked to fibrosis and cancer when overexpressed, while tumor suppression by the propeptide derived from pro-LOX has been documented. Similarly, in diabetic retinopathy, LOX overexpression, activity, and elevated LOX propeptide have been documented. The proteolytic processing of pro-forms of the respective proteins is beginning to draw attention as the resultant peptides appear to exhibit their own biological activities. In this review we focus on the LOX paralogue, and what is known regarding its extracellular biosynthetic processing and the still incomplete knowledge regarding the activities and mechanisms of the released lysyl oxidase propeptide (LOX-PP). In addition, a summary of the roles of both LOX and LOX-PP in diabetic retinopathy, and brief mentions of the roles for LOX and closely related LOXL1 in glaucoma, and keratoconus, respectively, are included.<\/jats:p>","DOI":"10.3390\/ijms23095088","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T08:21:25Z","timestamp":1651652485000},"page":"5088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Functions and Mechanisms of Pro-Lysyl Oxidase Processing in Cancers and Eye Pathologies with a Focus on Diabetic Retinopathy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5064-614X","authenticated-orcid":false,"given":"Philip C.","family":"Trackman","sequence":"first","affiliation":[{"name":"The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA"},{"name":"Department of Translational Dental Medicine, Boston University Henry M Goldman School of Dental Medicine, 700 Albany Street, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5793-0474","authenticated-orcid":false,"given":"Yaser","family":"Peymanfar","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayon","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1007\/s00018-006-6149-9","article-title":"Lysyl oxidase: An oxidative enzyme and effector of cell function","volume":"63","author":"Lucero","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12939","DOI":"10.1074\/jbc.274.18.12939","article-title":"The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues","volume":"274","author":"Tronecker","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0945-053X(01)00157-3","article-title":"Cloning and characterization of a fifth human lysyl oxidase isoenzyme: The third member of the lysyl oxidase-related subfamily with four scavenger receptor cysteine-rich domains","volume":"20","author":"Maki","year":"2001","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.matbio.2016.01.001","article-title":"Enzymatic and non-enzymatic functions of the lysyl oxidase family in bone","volume":"52\u201354","author":"Trackman","year":"2016","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0968-0004(94)90165-1","article-title":"The SRCR superfamily: A family reminiscent of the Ig superfamily","volume":"19","author":"Resnick","year":"1994","journal-title":"Trends Biochem. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevImmunol.v24.i1.10","article-title":"The Scavenger Receptor Cysteine-Rich (SRCR) domain: An ancient and highly conserved protein module of the innate immune system","volume":"24","author":"Sarrias","year":"2004","journal-title":"Crit. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22537","DOI":"10.1074\/jbc.M102352200","article-title":"Multiple Bone Morphogenetic Protein 1-related Mammalian Metalloproteinases Process Pro-lysyl Oxidase at the Correct Physiological Site and Control Lysyl Oxidase Activation in Mouse Embryo Fibroblast Cultures","volume":"276","author":"Uzel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48944","DOI":"10.1074\/jbc.M109499200","article-title":"Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1","volume":"276","author":"Borel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Meier, A.A., Moon, H.J., Toth, R.T., Folta-Stogniew, E., Kuczera, K., Middaugh, C.R., and Mure, M. (2021). Oligomeric States and Hydrodynamic Properties of Lysyl Oxidase-Like 2. Biomolecules, 11.","DOI":"10.3390\/biom11121846"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16970","DOI":"10.1074\/jbc.M117.798603","article-title":"Proteolytic processing of lysyl oxidase-like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV","volume":"292","author":"Basak","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1517\/14728222.2016.1151003","article-title":"Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer","volume":"20","author":"Trackman","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1126\/science.1697103","article-title":"Expression of gene rrg is associated with reversion of NIH 3T3 transformed by LTR-c-H-ras","volume":"249","author":"Contente","year":"1990","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1126\/science.1678898","article-title":"Lysyl oxidase and rrg messenger RNA","volume":"253","author":"Kenyon","year":"1991","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"40593","DOI":"10.1074\/jbc.M406639200","article-title":"The propeptide domain of lysyl oxidase induces phenotypic reversion of ras-transformed cells","volume":"279","author":"Palamakumbura","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1128\/MCB.01148-10","article-title":"The Ras Signaling Inhibitor LOX-PP Interacts with Hsp70 and c-Raf To Reduce Erk Activation and Transformed Phenotype of Breast Cancer Cells","volume":"31","author":"Sato","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1038\/onc.2009.203","article-title":"Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling","volume":"28","author":"Palamakumbura","year":"2009","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7384","DOI":"10.1074\/jbc.M109.033597","article-title":"Lysyl oxidase propeptide inhibits FGF-2-induced signaling and proliferation of osteoblasts","volume":"285","author":"Vora","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1128\/MCB.01426-10","article-title":"The lysyl oxidase propeptide interacts with the receptor-type protein tyrosine phosphatase kappa and inhibits beta-catenin transcriptional activity in lung cancer cells","volume":"31","author":"Kirsch","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1074\/jbc.M802612200","article-title":"The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells","volume":"284","author":"Zhao","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1002\/jcb.25893","article-title":"UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells","volume":"118","author":"Kirsch","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Vallet, S.D., Miele, A.E., Uciechowska-Kaczmarzyk, U., Liwo, A., Duclos, B., Samsonov, S.A., and Ricard-Blum, S. (2018). Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30190-6"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10426","DOI":"10.1038\/s41598-018-28745-8","article-title":"Inhibition of angiogenesis in endothelial cells by Human Lysyl oxidase propeptide","volume":"8","author":"Nareshkumar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_23","first-page":"5029","article-title":"Lysyl oxidase inhibition via \u03b2-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro","volume":"17","author":"Shi","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.3892\/or.2014.3044","article-title":"Expression of the lysyl oxidase propeptide in hepatocellular carcinoma and its clinical relevance","volume":"31","author":"Zheng","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molonc.2015.07.005","article-title":"Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide","volume":"10","author":"Ozdener","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1021\/bi902218p","article-title":"Characterization of recombinant lysyl oxidase propeptide","volume":"49","author":"Vora","year":"2010","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s12038-020-0010-4","article-title":"Dynamic conformational flexibility and molecular interactions of intrinsically disordered proteins","volume":"45","author":"Bhattarai","year":"2020","journal-title":"J. Biosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sato, S., Zhao, Y., Imai, M., Simister, P.C., Feller, S.M., Trackman, P.C., Kirsch, K.H., and Sonenshein, G.E. (2013). Inhibition of CIN85-Mediated Invasion by a Novel SH3 Domain Binding Motif in the Lysyl Oxidase Propeptide. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077288"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1600-0854.2010.01061.x","article-title":"Emerging roles of Ruk\/CIN85 in vesicle-mediated transport, adhesion, migration and malignancy","volume":"11","author":"Havrylov","year":"2010","journal-title":"Traffic"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.15407\/ubj88.01.119","article-title":"Transcriptional regulation of NOX genes express ion in human breast adenocarcinoma MCF-7 cells is modulated by adaptor protein Ruk\/CIN 85","volume":"88","author":"Bazalii","year":"2016","journal-title":"Ukr. Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"C2095","DOI":"10.1152\/ajpcell.00613.2006","article-title":"Intracellular distribution of the lysyl oxidase propeptide in osteoblastic cells","volume":"292","author":"Guo","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12079-017-0424-4","article-title":"Functional importance of lysyl oxidase family propeptide regions","volume":"12","author":"Trackman","year":"2018","journal-title":"J. Cell Commun. Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1093\/carcin\/bgy045","article-title":"A polymorphism in the lysyl oxidase propeptide domain accelerates carcinogen-induced cancer","volume":"39","author":"Emmerling","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Friesenhengst, A., Pribitzer-Winner, T., and Schreiber, M. (2014). Association of the G473A polymorphism and expression of lysyl oxidase with breast cancer risk and survival in European women: A hospital-based case-control study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105579"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1089\/gtmb.2011.0374","article-title":"Lysyl oxidase G473A polymorphism is associated with increased risk of ovarian cancer","volume":"16","author":"Wu","year":"2012","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1089\/dna.2010.1098","article-title":"Lysyl oxidase 473 G>A polymorphism and breast cancer susceptibility in Chinese Han population","volume":"30","author":"Ren","year":"2011","journal-title":"DNA Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/j.1600-0463.2011.02802.x","article-title":"Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a South Korean population","volume":"119","author":"Yoon","year":"2011","journal-title":"Acta Pathol. Microbiol. Et Immunol. Scand."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1089\/dna.2014.2490","article-title":"Lysyl oxidase genetic variants affect gene expression in cervical cancer","volume":"33","author":"Bu","year":"2014","journal-title":"DNA Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fraga, A., Ribeiro, R., Coelho, A., Vizca\u00edno, J.R., Coutinho, H., Lopes, J.M., Pr\u00edncipe, P., Lobato, C., Lopes, C., and Medeiros, R. (2017). Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer. BMC Urol., 17.","DOI":"10.1186\/s12894-017-0201-y"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00438-014-0896-3","article-title":"Lysyl oxidase rs1800449 polymorphism and cancer risk among Asians: Evidence from a meta-analysis and a case-control study of colorectal cancer","volume":"290","author":"Gao","year":"2015","journal-title":"Mol. Genet. Genom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ijbiomac.2017.05.050","article-title":"Impact of lysyl oxidase (G473A) polymorphism on diabetic foot ulcers","volume":"103","author":"Pichu","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/21623945.2016.1271511","article-title":"Lysyl oxidase propeptide promotes adipogenesis through inhibition of FGF-2 signaling","volume":"6","author":"Griner","year":"2017","journal-title":"Adipocyte"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6685","DOI":"10.1158\/0008-5472.CAN-08-4818","article-title":"A loss-of-function polymorphism in the propeptide domain of the LOX gene and breast cancer","volume":"69","author":"Min","year":"2009","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9391","DOI":"10.1007\/s11033-012-1803-9","article-title":"Lysyl oxidase polymorphisms and ischemic stroke\u2014A case control study","volume":"39","author":"Zhang","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1089\/dna.2011.1261","article-title":"Lysyl oxidase G473A polymorphism is associated with increased risk of coronary artery diseases","volume":"30","author":"Ma","year":"2011","journal-title":"DNA Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11087","DOI":"10.1074\/jbc.RA119.007806","article-title":"Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and ADAMTS2\/14 regulates collagen binding through a tyrosine sulfate domain","volume":"294","author":"Paradela","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"19549","DOI":"10.1074\/jbc.M300767200","article-title":"Transforming growth factor-beta induces secretion of activated ADAMTS-2. A procollagen III N-proteinase","volume":"278","author":"Wang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Leduc, C., Dupont, L., Joannes, L., Monseur, C., Baiwir, D., Mazzucchelli, G., Deroanne, C., Colige, A., and Bekhouche, M. (2021). In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.643178"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/gim.2015.188","article-title":"Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type","volume":"18","author":"Colige","year":"2016","journal-title":"Genet. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liang, L., Zhu, J.H., Chen, G., Qin, X.G., and Chen, J.Q. (2020). Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer. J. Oncol., 2020.","DOI":"10.1155\/2020\/9431560"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1177\/039463200501800311","article-title":"Potential markers of tongue tumor progression selected by cDNA microarray","volume":"18","author":"Carinci","year":"2005","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Li, G., Li, X., Yang, M., Xu, L., Deng, S., and Ran, L. (2017). Prediction of biomarkers of oral squamous cell carcinoma using microarray technology. Sci. Rep., 7.","DOI":"10.1038\/srep42105"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41389-019-0144-0","article-title":"Mechanism for oral tumor cell lysyl oxidase like-2 in cancer development: Synergy with PDGF-AB","volume":"8","author":"Mahjour","year":"2019","journal-title":"Oncogenesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3109\/02713683.2010.514659","article-title":"Vascular basement membrane thickening in diabetic retinopathy","volume":"35","author":"Roy","year":"2010","journal-title":"Curr. Eye Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"609","DOI":"10.2217\/imt.11.24","article-title":"Anti-inflammatory therapy for diabetic retinopathy","volume":"3","author":"Zhang","year":"2011","journal-title":"Immunotherapy"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/09286580701396720","article-title":"Overview of epidemiologic studies of diabetic retinopathy","volume":"14","author":"Klein","year":"2007","journal-title":"Ophthalmic. Epidemiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/414782a","article-title":"Global and societal implications of the diabetes epidemic","volume":"414","author":"Zimmet","year":"2001","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1517\/14712598.4.9.1395","article-title":"Ocular neovascularisation and excessive vascular permeability","volume":"4","author":"Campochiaro","year":"2004","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"86","DOI":"10.2337\/diabetes.55.01.06.db05-0186","article-title":"Effect of combined antisense oligonucleotides against high-glucose- and diabetes-induced overexpression of extracellular matrix components and increased vascular permeability","volume":"55","author":"Oshitari","year":"2006","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1002\/art.1780400813","article-title":"Collagen crosslinks in fibromyalgia","volume":"40","author":"Sprott","year":"1997","journal-title":"Arthritis Rheum."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1006\/abbi.1993.1151","article-title":"Expression and accumulation of lysyl oxidase, elastin, and type I procollagen in human Menkes and mottled mouse fibroblasts","volume":"301","author":"Gacheru","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1073\/pnas.69.9.2594","article-title":"Reducible crosslinks in hydroxylysine-deficient collagens of a heritable disorder of connective tissue","volume":"69","author":"Eyre","year":"1972","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/03008207509152341","article-title":"Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V","volume":"3","author":"Leachman","year":"1975","journal-title":"Connect. Tissue Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/0304-4165(79)90181-8","article-title":"Changes in lung lysyl oxidase activity in streptozotocin-diabetes and in starvation","volume":"585","author":"Madia","year":"1979","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1172\/JCI114807","article-title":"Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus","volume":"86","author":"Buckingham","year":"1990","journal-title":"J. Clin.Investig."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Daley, E.J., Pajevic, P.D., Roy, S., and Trackman, P.C. (2019). Impaired Gastric Hormone Regulation of Osteoblasts and Lysyl Oxidase Drives Bone Disease in Diabetes Mellitus. JBMR Plus, 3.","DOI":"10.1002\/jbm4.10212"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1007\/s00198-006-0155-5","article-title":"Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN\/Kob rats","volume":"17","author":"Saito","year":"2006","journal-title":"Osteoporos. Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"L29","DOI":"10.1152\/ajplung.00173.2020","article-title":"Lysyl Oxidase Directly Contributes to Extracellular Matrix Production and Fibrosis in Systemic Sclerosis","volume":"320","author":"Nguyen","year":"2020","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Bais, M.V., Nugent, M.A., Stephens, D.N., Sume, S.S., Kirsch, K.H., Sonenshein, G.E., and Trackman, P.C. (2012). Recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031188"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Yu, Z., Sato, S., Trackman, P.C., Kirsch, K.H., and Sonenshein, G.E. (2012). Blimp1 activation by AP-1 in human lung cancer cells promotes a migratory phenotype and is inhibited by the lysyl oxidase propeptide. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033287"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Subramanian, M.L., Stein, T.D., Siegel, N., Ness, S., Fiorello, M.G., Kim, D., and Roy, S. (2019). Upregulation of Lysyl Oxidase Expression in Vitreous of Diabetic Subjects: Implications for Diabetic Retinopathy. Cells, 8.","DOI":"10.3390\/cells8101122"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.2337\/db10-0365","article-title":"High glucose increases lysyl oxidase expression and activity in retinal endothelial cells: Mechanism for compromised extracellular matrix barrier function","volume":"59","author":"Chronopoulos","year":"2010","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1167\/iovs.16-21340","article-title":"Downregulation of Lysyl Oxidase Protects Retinal Endothelial Cells From High Glucose-Induced Apoptosis","volume":"58","author":"Kim","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1167\/iovs.18-25543","article-title":"Inhibition of Diabetes-Induced Lysyl Oxidase Overexpression Prevents Retinal Vascular Lesions Associated With Diabetic Retinopathy","volume":"59","author":"Song","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.exer.2019.04.019","article-title":"Decreased lysyl oxidase level protects against development of retinal vascular lesions in diabetic retinopathy","volume":"184","author":"Kim","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1167\/iovs.07-1550","article-title":"Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment","volume":"49","author":"Coral","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1442-9071.2004.00805.x","article-title":"Morphological changes in keratoconus: Pathology or pathogenesis","volume":"32","author":"Sherwin","year":"2004","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.clae.2010.04.006","article-title":"Keratoconus: A review","volume":"33","author":"Wolffsohn","year":"2010","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1167\/iovs.15-18105","article-title":"An Evaluation of Lysyl Oxidase-Derived Cross-Linking in Keratoconus by Liquid Chromatography\/Mass Spectrometry","volume":"57","author":"Takaoka","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_80","first-page":"12","article-title":"Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity","volume":"21","author":"Shetty","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s00702-013-0993-1","article-title":"The impairment of lysyl oxidase in keratoconus and in keratoconus-associated disorders","volume":"120","author":"Dudakova","year":"2013","journal-title":"J. Neural. Transm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3109\/13816810.2014.881507","article-title":"Association of Lysyl oxidase (LOX) Polymorphisms with the Risk of Keratoconus in an Iranian Population","volume":"36","author":"Saravani","year":"2015","journal-title":"Ophthalmic. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1167\/iovs.11-9268","article-title":"Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies","volume":"53","author":"Bykhovskaya","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1167\/iovs.02-0671","article-title":"Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays","volume":"44","author":"Nielsen","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/eye.2015.63","article-title":"Keratoconus: An inflammatory disorder?","volume":"29","author":"Galvis","year":"2015","journal-title":"Eye"},{"key":"ref_86","first-page":"2482","article-title":"Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus","volume":"17","author":"Laborante","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1167\/iovs.08-2173","article-title":"Localization of a gene for keratoconus to a 5.6-Mb interval on 13q32","volume":"50","author":"Gajecka","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1177\/1120672118795405","article-title":"Lack of association between lysyl oxidase-like 1 polymorphism in pseudoexfoliation syndrome and pseudoexfoliation glaucoma in North Indian population","volume":"29","author":"Pandav","year":"2019","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_89","first-page":"550","article-title":"Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma: A meta-analysis","volume":"7","author":"Sun","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1097\/IJG.0000000000001475","article-title":"Prevalence of Pseudoexfoliation Glaucoma Risk-associated Variants Within Lysyl Oxidase-like 1 in an Irish Population","volume":"29","author":"Eivers","year":"2020","journal-title":"J. Glaucoma"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1097\/IJG.0000000000000672","article-title":"Association of Lysyl Oxidase-like 1 Gene Polymorphism in Turkish Patients With Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma","volume":"26","author":"Palamar","year":"2017","journal-title":"J. Glaucoma"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1097\/IJG.0000000000000557","article-title":"Association of Lysyl Oxidase-Like 1 Gene Polymorphism in Turkish Patients With Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma","volume":"26","author":"Asfuroglu","year":"2017","journal-title":"J. Glaucoma"},{"key":"ref_93","first-page":"25","article-title":"Association of Lysyl Oxidase-Like 1 Gene Polymorphisms in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in a Spanish Population","volume":"37","year":"2016","journal-title":"Ophthalmic. Genet."},{"key":"ref_94","first-page":"1446","article-title":"Association of lysyl oxidase-like 1 gene common sequence variants in Greek patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma","volume":"19","author":"Metaxaki","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/IJG.0b013e31819f9330","article-title":"Lysyl oxidase-like 1 gene polymorphisms in German patients with normal tension glaucoma, pigmentary glaucoma and exfoliation glaucoma","volume":"19","author":"Wolf","year":"2010","journal-title":"J. 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