Follistatin-like 3 suppresses cell proliferation and fibronectin expression via p38MAPK pathway in rat mesangial cells cultured under high glucose.

Abstract

Mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation are early features of diabetic nephropathy. Follistatin-like 3 (FSTL3), a member of follistatin family, has been shown to regulate insulin and glucagon sensitivities in diet-induced obesity and insulin resistance. However, the role of FSTL3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of FSTL3 on cell proliferation and ECM accumulation expression in rat MCs cultured under high glucose, and elucidated the underlying mechanism. We found that the expression of FSTL3 was decreased significantly in MCs cultured high glucose condition. Overexpression of FSTL3 inhibited high glucose-induced MC proliferation and blocked the G1/S phase transition under high glucose condition. And, FSTL3 overexpression also reduced the expression of α-smooth muscle actin (α-SMA) and fibronectin (FN) induced by high glucose. Furthermore, overexpression of FSTL3 suppressed high-glucose-induced p38 phosphorylation in MCs. Taken together, our present study demonstrated that FSTL3 suppressed high glucose-induced MC proliferation and ECM accumulation via inhibiting the p38MAPK signaling pathway, and that FSTL3 may be a potential therapeutic target for the treatment of diabetic nephropathy.