Effect of simvastatin on expression of transforming growth factor-β and collagen type IV in rat mesangial cells.

Objective: Diabetic nephropathy is characterized by the accumulation of extracellular matrix in the glomerular mesangium as a result of an imbalance between matrix synthesis and degradation. Since simvastatin has been proposed to decrease renal interstitial fibrosis, we hypothesized that the protective effect of statins was related to the expression of transforming growth factor-β (TGF-β) and type IV collagen (Col IV).

Methods: Cultured rat mesangial cells (RMC) were exposed to high glucose (HG), advanced glycosylation end products (AGE) or H(2)O(2) in the absence and presence of simvastatin. Expression of TGF-β and Col IV was determined by Western blotting.

Results: Coincubation of RMC with HG, AGE or H(2)O(2) resulted in a significant increase of the expression of TGF-β and Col IV (p < 0.05). Simvastatin significantly inhibited HG-, AGE- or H(2)O(2)-induced expression of TGF-β and Col IV (p < 0.05). Moreover, simvastatin also inhibited HG-, AGE- and H(2)O(2)-induced activation of p38 mitogen-activated protein kinase, which indicated that the preventive effect of simvastatin on TGF-β and Col IV may be associated with p38.

Conclusion: These findings suggest that simvastatin can reduce HG-, AGE- and H(2)O(2)-induced expression of TGF-β and Col IV by inhibition of the p38 pathway.