Proteasome inhibitor MG132 inhibits the process of renal interstitial fibrosis.

Abstract

The proteasome inhibitor pathway serves a crucial role in cell cycle progression and apoptosis, and in the activation of transcription factors and cytokines in tumor cells. The aim of the current study was to investigate the effect of the proteasome inhibitor, MG132, on transforming growth factor (TGF)-β1-induced expression of extracellular matrix proteins in rat renal interstitial fibroblasts (NRK-49F cells) and to better elucidate the mechanism by which MG132 functions. The level of connective tissue growth factor (CTGF), α-smooth muscle actin (SMA), fibronectin (FN) and collagen type III (Col III) in the MG132-pretreated groups was significantly decreased compared with groups treated with TGF-β1 alone. MG132 significantly decreased mRNA and the protein levels of fibrosis-associated factors induced by TGF-β1 treatment. The MG132-pretreated groups exhibited lower phosphorylated-mothers against decapentaplegic homolog (p-Smad)2, p-Smad3 and FN protein expression compared with the groups treated with TGF-β1 alone. In conclusion, MG132 reduced mRNA and protein expression of fibrosis-associated factors. It can successfully inhibit the inflammatory reaction induced by TGF-β via the Smad signaling pathway. These results indicate that MG132 appears to have a potent effect in counteracting renal fibrosis. MG132 may be applied in the treatment of patients with chronic kidney disease.