Oxidative stress enhanced the transforming growth factor-?2-induced epithelial-mesenchymal transition through chemokine ligand 1 on ARPE-19 cell.

ABSTRACT: Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness. The effect of oxidative stress alone or together with transforming growth factor-beta 2 (TGF-?2) on epithelial-mesenchymal transformation (EMT) is not fully understood in RPE. TGF-?2 induced the upregulation EMT markers including ?-smooth muscle actin (?-SMA), Snail, and Slug and downregulation of E-cadherin (E-cad) in ARPE-19 cells. Hydrogen peroxide (H2O2) not only upregulated ?-SMA but also enhanced the effect of TGF-?2 on the expression of Snail and Slug. The CXCL family of cytokines could be the mediators of EMT induced by H2O2 and TGF-?2. H2O2 induced CXCL1, that upregulated ?-SMA and fibronectin. Both SB225002, an inhibitor of CXCR2, and antioxidant N-acetylcysteine suppressed the TGF-?2-induced EMT in ARPE-19 cells. Taken together, the results suggest that oxidative stress enhanced TGF-?2-induced EMT through the possible autocrine effect of CXCL1 on CXCR2 in ARPE-19 cells.

SUBMITTER: Yang IH 

PROVIDER: S-EPMC7055234 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature