title: Notch signal regulates corneal endothelial-to-mesenchymal transition.
abstract: Endothelial-to-mesenchymal transition (EnMT) is a cell transformation process involved in both morphogenesis and pathogenesis. EnMT of corneal endothelial cells happens after endothelial injury and during ex vivo culture. Previous studies have shown that the transforming growth factor-β signaling pathway is involved in this transition. In this study, we found that rat corneal endothelial cells could spontaneously undergo EnMT during ex vivo culture. This change in rat corneal endothelial cells was associated with Notch signaling pathway activation after the first passage, which was blocked by the Notch inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). This inhibitor also prevented transforming growth factor β1-, β2-, and β3-induced EnMT and reversed transformed rat corneal endothelial cells to a normal phenotype. Furthermore, DAPT treatment blocked retrocorneal membrane formation in a rat corneal endothelium damage model. Our study indicates that the Notch signaling pathway is involved in the corneal EnMT process, which may be a novel therapeutic target for treating corneal endothelial fibrogenic disorders.
authors.affiliation: Eye Institute of Xiamen University, Xiamen, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.forename: Yanni
authors.initials: Y
authors.lastname: Jia
authors.forename: Huiyi
authors.initials: H
authors.lastname: Du
authors.forename: Nuo
authors.initials: N
authors.lastname: Dong
authors.forename: Yajie
authors.initials: Y
authors.lastname: Xu
authors.forename: Shen
authors.initials: S
authors.lastname: Wang
authors.forename: Huping
authors.initials: H
authors.lastname: Wu
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003316:Corneal Diseases / Q000235:genetics / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004728:Endothelium, Corneal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta