Role of aldose reductase in TGF-beta1-induced fibronectin synthesis in human mesangial cells.

Accumulation of glomerular extracellular matrix (ECM) may result in glomerulosclerosis. Several lines of evidence indicate a key role for transforming growth factor-beta1 (TGF-beta1) in glomerular ECM synthesis and degradation, such as fibronectin (FN). Aldose reductase (AR) was proven to be one of the TGF-beta1 responsive genes in cultured rat mesangial cells using the SSH-PCR method and there were positive correlation between the AR and TGF-beta1 in our previous studies. So we assumed that AR could regulate FN synthesis. In this study, we explored the role of AR in FN production and possible mechanism involved. The expression of AR, FN and c-Jun proteins were analyzed by Western blot and the activity of activator protein-1 (AP-1) was assessed by electrophoretic mobility shift assay (EMSA). Our results showed that AR could mediate the TGF-beta1-induced FN production, which may associate with AP-1 activation.