The role of HIF-1α in the TGF-β2-mediated epithelial-to-mesenchymal transition of human lens epithelial cells

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 (10ng/mL, 48h) 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 10ng/mL) did not alter the EMT marker levels in HLE. Addition of a prolyl hydroxylase inhibitor, dimethyloxalylglycine (DMOG, up to 10 mu M), 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.