In vitro inhibition of proliferation, migration and epithelial-mesenchymal transition of human lens epithelial cells by fasudil

Abstract

AIM: To study the potential role of fasudil as a treatment for posterior capsular opacification (PCO) of the human crystalline lens. METHODS: Human lens epithelial cells (HLECs; line SRA01/04) was exposed to transforming growth factor-β2 (TGF-β2) to induce the process of epithelial-mesenchymal transition (EMT). Fasudil was applied to the cell samples. Its effect on overall HLECs proliferation and migration was studied, as was its influence on EMT induction by TGF-β2 using cell migration assay, MTT colorimetric assay and Western blot assay. RESULTS: Fasudil inhibited the proliferation of SRA01/04. Its effect was time- and concentration-dependent. The migration of SRA01/04 cells was significantly reduced 24-72h after fasudil treatment, and the half maximal inhibitory concentration (IC50) was 22.37 μmol/mL at 72h. Reversal of the elongated, fibroblast-like shape changes induced by TGF-β2 in SRA01/04 cells was observed. Fasudil up-regulated the expression of Connexin43 protein and down-regulated the expression of α-SMA protein compared with the cells treated with TGF-β2. Furthermore, when exposed to fasudil, the phosphorylation of Rho-associated protein kinase (Rock) and myosin light chain (MLC) could not be activated in the cell preparations. CONCLUSION: Fasudil suppresses the proliferation and migration of SRA01/04 cells, and inhibits the process of EMT induced by TGF-β2. These results suggest that fasudil may serve as a therapeutic agent for PCO.

Keywords

• 1257
• fasudil
• human lens epithelial cells
• TGF-β2
• Rho/Rock
• epithelial-mesenchymal transition