The role of HIF-1? in the TGF-?2-mediated epithelial-to-mesenchymal transition of human lens epithelial cells.

ABSTRACT: Human lens epithelial cells (HLE) undergo mesenchymal transition and become fibrotic during posterior capsule opacification (PCO), which is a frequent complication after cataract surgery. TGF-?2 has been implicated in this fibrosis. Previous studies have focused on the role of hypoxia-inducible factor-1? (HIF-1?) in fibrotic diseases, but the role of HIF-1? in the TGF-?2-mediated fibrosis in HLE is not known. TGF-?2 treatment (10?ng/mL, 48?h) increased the HIF-1? levels along with the EMT markers in cultured human lens epithelial cells (FHL124 cells). The increase in HIF-1? corresponded to an increase in VEGF-A in the culture medium. However, exogenous addition of VEGF-A (up to 10?ng/mL) did not alter the EMT marker levels in HLE. Addition of a prolyl hydroxylase inhibitor, dimethyloxalylglycine (DMOG, up to 10?µM), enhanced the levels of HIF-1?, and secreted VEGF-A but did not alter the EMT marker levels. However, treatment of cells with a HIF-1? translational inhibitor, KC7F2, significantly reduced the TGF-?2-mediated EMT response. This was accompanied by a reduction in the ERK phosphorylation and nuclear translocation of Snail and Slug. Together, these data suggest that HIF-1? is important for the TGF-?2-mediated EMT of human lens epithelial cells.

SUBMITTER: Nahomi RB 

PROVIDER: S-EPMC6605039 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature