αB-crystallin is essential for the TGF-β2-mediated epithelial to mesenchymal transition of lens epithelial cells.
Transforming growth factor (TGF)-β2-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 αB-crystallin is a major protein in LEC, its role in the EMT remains unknown. In a human LEC line (FHL124), TGF-β2 treatment resulted in changes in the EMT-associated proteins at the mRNA and protein levels. This was associated with nuclear localization of αB-crystallin, phosphorylated Smad2 (pSmad2) (S245/250/255), pSmad3 (S423/425), Smad4 and Snail and the binding of αB-crystallin to these transcription factors, all of which were reduced by the down-regulation of αB-crystallin. Expression of the functionally defective R120G mutant of αB-crystallin reduced TGF-β2-induced EMT in LECs of αB-crystallin knockout (KO) mice. Treatment of bovine lens epithelial explants and mouse LEC with TGF-β2 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 αB-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 αB-crystallin KO mice. Together, our data show that αB-crystallin plays a central role in the TGF-β2-induced EMT of LEC. αB-Crystallin could be targeted to prevent PCO and pathological fibrosis in other tissues.
['Nahomi|Rooban B|RB|', 'Pantcheva|Mina B|MB|', 'Nagaraj|Ram H|RH|']
D000818:Animals D002417:Cattle D002460:Cell Line D003459:Crystallins D004847:Epithelial Cells D058750:Epithelial-Mesenchymal Transition D006367:HeLa Cells D006801:Humans D007908:Lens, Crystalline D051379:Mice D018345:Mice, Knockout D015398:Signal Transduction D051899:Smad2 Protein D051900:Smad3 Protein D051901:Smad4 Protein D000071250:Snail Family Transcription Factors D053781:Transforming Growth Factor beta2
αB-crystallin epithelial to mesenchymal transition lens epithelial cells TGF-β2