Proteasome inhibitor inhibits proliferation and induces apoptosis in renal interstitial fibroblasts

Background: the ubiquitin proteasome pathway plays a pivotal role in controlling cell proliferation,apoptosis and differentiation in a variety of normal and tumor cells. this study aimed to investigate the role of a proteasome inhibitor on proliferation,apoptosis and related proteins in renal interstitial fibroblasts (nrk-49f). methods: nrk-49f cells were induced using transforming growth factor-b1 (tgf-b1) and pretreated with the proteasome inhibitor mg-132. cell proliferation was measured using 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (mtt). the cell cycle and apoptosis were analyzed using flow cytometry. apoptosis was also analyzed using a dnaladder. the protein expression of p53,p27,p21,caspase-3,bcl-2 and bax was examined using western blots. results: the results showed that tgf-b1 (5 ng/ml) can stimulate the proliferation of nrk-49f cells.mg-132 (0.25-5 μm) inhibited tgf-b1-induced proliferation in a dose-dependent manner through g1-arrest; tgf-b1 alone did not induce apoptosis (3.8 ± 0.4% vs. 4.7 ± 1.6%). however,pretreatment with mg-132 significantly induced apoptosis in tgf-b1-stimulated nrk-49f cells in a dosedependentmanner. atypicaldnaladderwas also confirmed in these two groups.western blot analysis showed thatmg-132 activated p53,p21,caspase-3 and bax,and inhibited bcl-2 in a dose-dependent manner,while p27 expression remained unchanged. conclusions: a proteasome inhibitor inhibited proliferation and induced apoptosis in renal interstitial fibroblasts stimulated by tgf-b1. the mechanism may relate to the p53,p21,caspase-3,bcl-2 and bax pathways. our results suggest that a proteasome inhibitor could be a new strategy to treat renal interstitial fibrosis. copyright © 2013 by institute of pharmacology polish academy of sciences.