Objective: To study the effects of aldose reductase (AR) on the proliferation of rat mesangial cells (MsC) in vitro and to investigate its mechanism.
Methods: Cell proliferation was assessed by MTT colorimetric assay. Cell cycle and apoptosis were analyzed by flow cytometry. The growth of normal MsC and AR transfected MsC was compared. The proliferation of PDGF-BB and cellular growth stimulation by 10% NBS were investigated using AR inhibitors (ARI) Sorbinil and Zopolrestat. The effects of PDGF-BB on the expression of AR, p65 and c-Jun were assessed by Western blot. Activation of AP-1 was measured by EMSA.
Results: AR expression of transfected MsC was distinctly higher than that of the control. Transfected MsC grew quicker than normal cells. ARI partially inhibited the proliferation of transfected MsC under the stimulation of PDGF-BB and 10% NBS, whereas 10% NBS had no effect on normal MsC. PDGF-BB upregulated the expression of AR and c-Jun, but had no effect on p65. The upregulation of c-Jun and the activation of AP-1 could be attenuated by ARI.
Conclusion: AR may participate in the pathological proliferation of MsC through the pathway related to the activation of AP-1.