Rho/myocardin-related transcription factor A (MRTF-A) pathway plays an important role in TGF-β-induced epithelial mesenchymal transition in retinal pigment epithelial cells

Abstract

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is associated with ocular fibrotic conditions such as proliferative vitreoretinopathy and wet/neovascular type age-related macular degeneration. Upon transforming growth factor-β (TGF-β) stimulation, myocardin-related transcription factor A (MRTF-A) is translocated from the cytoplasm into the nucleus via Rho activation to promote EMT in various cells. However, it is unknown whether the Rho/MRTF pathway is involved in the EMT of TGF-β-induced RPE cells. In this study, TGF-β2 led to an increase in mRNA expression of α-smooth muscle actin (α-SMA), a biomarker of EMT, and type I collagen, repressed by MRTF-A knockdown, in human retinal pigment epithelial (ARPE-19) cells. CCG-203971, an MRTF-A inhibitor, also downregulated the mRNA expression ofα-SMA and type I collagen in TGF-β2-treated ARPE-19 cells via a reduction in MRTF-A nuclear translocation. Moreover, Y-27632, a Rho-associated protein kinase inhibitor, inhibited the expression ofα-SMA and type I collagen and suppressed the translocation of MRTF-A to the nucleus in TGF-β-treated ARPE-19 cells. These results suggest that the Rho/MRTF pathway plays an important role in the EMT of TGF-β-induced RPE cells.