αB-crystallin is essential for the TGF-ß2-mediated epithelial to mesenchymal transition of lens epithelial cells.
Biochem J
; 473(10): 1455-69, 2016 05 15.
Article
in En
| MEDLINE
| ID: mdl-26987815
ABSTRACT
Transforming growth factor (TGF)-ß2-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-ß2 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-ß2-induced EMT in LECs of αB-crystallin knockout (KO) mice. Treatment of bovine lens epithelial explants and mouse LEC with TGF-ß2 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-ß2-induced EMT of LEC. αB-Crystallin could be targeted to prevent PCO and pathological fibrosis in other tissues.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Crystallins
/
Epithelial Cells
/
Transforming Growth Factor beta2
/
Epithelial-Mesenchymal Transition
/
Lens, Crystalline
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem J
Year:
2016
Type:
Article
Affiliation country:
United States