Proteasome inhibitor inhibits proliferation and induces apoptosis in renal interstitial fibroblasts.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 5
Abstract
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-β1 (TGF-β1) 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 DNA ladder. The protein expression of p53, p27, p21, caspase-3, Bcl-2 and Bax was examined using western blots. Results: The results showed that TGF-β1 (5 ng/ml) can stimulate the proliferation of NRK-49F cells.MG-132 (0.25-5 μM) inhibited TGF-β1-induced proliferation in a dose-dependent manner through G1-arrest; TGF-β1 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 dose-dependent manner. A typical DNA ladder was also confirmed in these two groups. Western blot analysis showed that MG-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-β1. 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.
Authors and Affiliations
Bingbing Zhu, Yuanmeng Jin, Lin Han, Hui Chen, Fang Zhong, Weiming Wang, Nan Chen
Keywords
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