Transforming growth factor-β2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of RAGE

Transforming growth factor-beta 2 (TGF beta 2)-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 TGF beta 2-mediated EMT in LECs. Unlike in the LECs from wild-type mice, TGF beta 2 failed to elicit an EMT response in LECs from RAGE knockout mice. The lack of RAGE also diminished TGF beta 2-mediated Smad signaling. In addition, treatment with TGF beta 2 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 TGF beta 2-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 alpha-smooth muscle actin (alpha-SMA), fibronectin (FN), and integrin beta 1 in capsule-adherent LECs. Taken together, these results suggest that TGF beta 2 signaling is intricately linked to RAGE. Targeting RAGE could be explored as a therapeutic strategy against secondary cataracts.

Automated summary

The study revealed a close relationship between TGF beta 2 signaling and RAGE in LECs, with knockout of RAGE attenuating the EMT response mediated by TGF beta 2. Targeting RAGE could be considered as a therapeutic strategy against secondary cataracts.