Transforming growth factor-ß2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of RAGE.

ABSTRACT

Transforming growth factor-ß2 (TGFß2)-mediated epithelial to mesenchymal transition (EMT) in lens epithelial cells (LECs) has been implicated in fibrosis associated with secondary cataracts. In this study, we investigated whether the receptor for advanced glycation end products (RAGE) plays a role in TGFß2-mediated EMT in LECs. Unlike in the LECs from wild-type mice, TGFß2 failed to elicit an EMT response in LECs from RAGE knockout mice. The lack of RAGE also diminished TGFß2-mediated Smad signaling. In addition, treatment with TGFß2 increased IL-6 levels in LECs from wild-type mice but not in those from RAGE knockout mice. Treatment of human LECs with the RAGE inhibitor FPS-ZM1 reduced TGFß2-mediated Smad signaling and the EMT response. Unlike that in wild-type lenses, the removal of fiber cell tissue in RAGE knockout lenses did not result in elevated levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and integrin ß1 in capsule-adherent LECs. Taken together, these results suggest that TGFß2 signaling is intricately linked to RAGE. Targeting RAGE could be explored as a therapeutic strategy against secondary cataracts.