The role of HIF‐1α in the TGF‐β2‐mediated epithelial‐to‐mesenchymal transition of human lens epithelial cells. Issue 8 (25th April 2018)

• Record Type: Journal Article
• Authors: Nahomi, Rooban B.; Nagaraj, Ram H.
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 8(2018)
• Page Start: 6814
• Page End: 6827
• Publication Date: 2018-04-25
• Subjects: epithelial‐to‐mesenchymal transition -- HIF‐1α -- KC7F2 -- lens epithelial cells -- TGF‐β2 -- VEGF‐A; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26877
• Languages: English
• ISSNs: 0730-2312

Abstract

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. Abstract : HIF‐1α and VEGF‐A were upregulated during TGF‐β2‐mediated EMT of human lens epithelial cells. In the absence of TGF‐β2, overexpression of HIF‐1α or exogenous addition of VEGF‐A to lens epithelial cell culture failed to induce the EMT response. TGF‐β2‐mediated EMT was inhibited by the treatment of a HIF‐1α translational inhibitor (KC7F2). The effect of KC7F2 was through reductions in ERK phosphorylation and nuclear translocation of Snail and Slug. A HIF‐1α translational inhibitor KC7F2 was able to inhibit the TGF‐β2‐mediated upregulation of the epithelial to mesenchymal transition (EMT) markers in human lens epithelial cells. Based on our findings, we propose that HIF‐1α is important for the TGF‐β2‐mediated EMT of human lens epithelial cells.