Role of aldose reductase in the high glucose induced expression of fibronectin in human mesangial cells.

Aldose reductase (AR) has emerged as a key contributor to the diabetic nephropathy (DN), however, the mechanisms by which AR increases DN remain poorly understood. Here, we report that exposure to high glucose (HG) stimulates fibronectin (FN) from human mesangial cells in culture. Our results show that exposure to HG and overexpression AR increase the expression of FN. This increase was prevented by the AR inhibitors sorbinil and zopolrestat. Treatment with HG and transfected with plasmid PcDNA3.0-AR, resulted in phosphorylation and activation of ERK, JNK and AKT signaling pathway, and increase the expression of FN. Treatment with inhibitor of JNK and AKT signaling pathway decreased the expression of FN. These results show that inhibition of AR may be useful to prevented extracellular matrix (ECM) deposition in diabetic nephropathy, which is regulated by JNK and AKT.