First Author | Nahomi RB | Year | 2016 |
Journal | Biochem J | Volume | 473 |
Issue | 10 | Pages | 1455-69 |
PubMed ID | 26987815 | Mgi Jnum | J:245447 |
Mgi Id | MGI:5916597 | Doi | 10.1042/BCJ20160128 |
Citation | Nahomi RB, et al. (2016) alphaB-crystallin is essential for the TGF-beta2-mediated epithelial to mesenchymal transition of lens epithelial cells. Biochem J 473(10):1455-69 |
abstractText | Transforming growth factor (TGF)-beta2-mediated pathways play a major role in the epithelial to mesenchymal transition (EMT) of lens epithelial cells (LECs) during secondary cataract formation, which is also known as posterior capsule opacification (PCO). Although alphaB-crystallin is a major protein in LEC, its role in the EMT remains unknown. In a human LEC line (FHL124), TGF-beta2 treatment resulted in changes in the EMT-associated proteins at the mRNA and protein levels. This was associated with nuclear localization of alphaB-crystallin, phosphorylated Smad2 (pSmad2) (S245/250/255), pSmad3 (S423/425), Smad4 and Snail and the binding of alphaB-crystallin to these transcription factors, all of which were reduced by the down-regulation of alphaB-crystallin. Expression of the functionally defective R120G mutant of alphaB-crystallin reduced TGF-beta2-induced EMT in LECs of alphaB-crystallin knockout (KO) mice. Treatment of bovine lens epithelial explants and mouse LEC with TGF-beta2 resulted in changes in the EMT-associated proteins at the mRNA and protein levels. This was accompanied by increase in phosphorylation of p44/42 mitogen-activated protein kinases (MAPK) (T202/Y204), p38 MAPK (T180/Y182), protein kinase B (Akt) (S473) and Smad2 when compared with untreated cells. These changes were significantly reduced in alphaB-crystallin depleted or knocked out LEC. The removal of the fibre cell mass from the lens of wild-type (WT) mice resulted in the up-regulation of EMT-associated genes in the capsule-adherent epithelial cells, which was reduced in the alphaB-crystallin KO mice. Together, our data show that alphaB-crystallin plays a central role in the TGF-beta2-induced EMT of LEC. alphaB-Crystallin could be targeted to prevent PCO and pathological fibrosis in other tissues. |