Basic & Clinical Medicine ›› 2014, Vol. 34 ›› Issue (2): 160-167.

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Proteasome inhibitor MG132 improves the renal tubule-interstitium in diabetic rats


  • Received:2013-07-01 Revised:2013-09-26 Online:2014-02-05 Published:2014-01-13
  • Contact: Bing GUO,

Abstract: Objective To investigate proteasome inhibitor MG132 whether or not to reduce or slow down the renal tubule-interstitium during diabetic nephropathy (DN). Methods The diabetic rat model(DM) was established by injecting Streptozotocin(STZ) (n = 10). Meanwhile, ten rats were grouped into normal control group (NC). After 24 weeks, the rats were sacrificed to detect relevant biochemical parameters, and to observe the changes of pathomorphology of kidney and pancreas as well. NRK-52E cells were cultured in vitro, to be pre-treated with different doses MG132 cultured in high glucose. In addition, immunohistochemistry and immunofluorescence staining, Western blotting were employed to detect the protein expression of Smad7, Smad ubiquitin regulatory factor 2(Smurf2), E-cadherin (E-cadherin) and α-smooth muscle actin (α-SMA) and fibronectin (FN), collagen-Ⅰ (Col-1)in the renal tissue and NRK-52E cells. Results Compared with NC group,the expression of E-cadherin decreased and α-SMA increased in DM group (P <0.05). In DM group, the expressions of FN and Col-1 in renal interstitium were increased (P < 0.05), while the protein expression of Smad7decreased (P <0.05),but Smurf2 was increased (P <0.05). In vitro, MG132 inhibited the protein expressions of α-SMA and Col-Ⅰby a dose-dependent manner which were induced by high glucose in NRK-52E cells (P <0.05), but it had no effect with the protein expression of Smurf2.In contrary, MG132 increased the protein expression of Smad7 and E-cadherin (P <0.05). Conclusion MG132 inhibited the protein degradation of Smad7 which high glucose-mediated, could reduce the development of the renal tubule-interstitium, this may be one of the mechanisms that MG132 could treat DN.

Key words: Diabetic nephropathy, Renal fibrosis, Smad7, MG132

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