Aldose reductase is a potent regulator of TGF-β1 induced expression of fibronectin in human mesangial cells

Glomerulosclerosis is considered to be the final pathway leading to the progressive loss of renal function in several kidney diseases, transforming growth factor beta 1 (TGF-beta 1) plays a critical role in glomerulosclerosis. However, the mechanisms of TGF-beta 1 stimulating glomerulosclerosis remain poorly understood. Here we report that TGF-beta 1-induced expression of fibronectin (FN) depends on the activity of aldose reductase (AR) in human mesangial cells (HMCs). The results show that TGF-beta 1 increased the expression of FN, which attenuated by pharmacological inhibition of AR or knockdown of the enzyme by small interfering RNA (siRNA). MAPKs (ERK, JNK and p38) signalling pathways were activated in HMCs after stimulated by TGF-beta 1, inhibition of AR blunted the activation ERK, p38 and JNK signalling pathways. These changes were associated with decreased TGF-beta 1-induced expression of FN. These results indicate that AR is a potent regulator of TGF-beta 1 induced expression of FN in human mesangial cells: it suggests that inhibition of this enzyme may be useful to prevented extracellular matrix (ECM) deposition in glomerulosclerosis.