The role of HIF‐1α in the TGF‐β2‐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-β2 has been implicated in this fibrosis. Previous studies have focused on the role of hypoxia-inducible factor-1α (HIF-1α) in fibrotic diseases, but the role of HIF-1α in the TGF-β2-mediated fibrosis in HLE is not known. TGF-β2 treatment (10 ng/mL, 48 h) increased the HIF-1α levels along with the EMT markers in cultured human lens epithelial cells (FHL124 cells). The increase in HIF-1α 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-1α, and secreted VEGF-A but did not alter the EMT marker levels. However, treatment of cells with a HIF-1α translational inhibitor, KC7F2, significantly reduced the TGF-β2-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-1α is important for the TGF-β2-mediated EMT of human lens epithelial cells.