HuangQi Decoction Ameliorates Renal Fibrosis via TGF-β/Smad Signaling Pathway In Vivo and In Vitro

被引:48
作者
Zhao, Jie [1 ]
Wang, Li [2 ]
Cao, Ai-li [2 ]
Jiang, Ming-Qian [1 ]
Chen, Xia [1 ]
Wang, Yi [1 ]
Wang, Yun-man [1 ]
Wang, Hao [1 ]
Zhang, Xue-Mei [3 ]
Peng, Wen [1 ,2 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Nephrol, Shanghai, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Lab Renal Dis, Shanghai, Peoples R China
[3] Fudan Univ, Sch Pharm, Dept Pharmacol, 826 Zhangheng Rd, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
HuangQi decoction; TGF-beta/Smad signaling pathway; LUG model; Renal interstitial fibrosis; EPITHELIAL-MESENCHYMAL TRANSITION; UNILATERAL URETERAL OBSTRUCTION; INTERSTITIAL FIBROSIS; TUBULOINTERSTITIAL FIBROSIS; DIABETIC-NEPHROPATHY; KIDNEY FIBROSIS; IMMUNOHISTOCHEMISTRY APPLICATIONS; MOLECULAR-MECHANISMS; TUBULAR CELLS; UP-REGULATION;
D O I
10.1159/000443115
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective: Traditional Chinese Medicine compound HuangQi decoction is widely used in clinical treatment of chronic kidney disease, but its role on renal interstitial fibrosis and the underlying mechanism remains unclear. The aim of this study is to investigate the effect of HuangQi decoction on renal interstitial fibrosis and its association with the TGF-beta/Smad signaling pathway. Methods: A total of 120 C57/BL mice were randomly divided into six groups: sham group, sham plus high-dose HuangQi decoction (1.08g/kg) group, unilateral ureteral obstruction ((JUG) model group, and (JUG model plus low to high doses of HuangQi decoction (0.12g /kg, 0.36g/kg and 1.08g/kg respectively) groups. Animals were sacrificed 14 days after the administration and ipsilateral kidney tissue was sampled for pathologic examinations. Immunohistochemistry, PCR and western blot were used to detect the expressions of related molecules in the TGF-beta/Smad signaling pathway. TGF-beta 1 was used in in vitro experiments to induce human kidney proximal tubule epithelial cells (HK2). Results: HuangQi decoction improved ipsilateral kidney fibrosis in (JUG mice and downregulated the expressions of TGF-beta 1, T beta RI, T beta RII, Smad4, Smad2/3, P-Smad2/3, alpha-SMA, collagen type I, III and IV in a dose-dependent manner while upregulated the expression of Smad7 in the same fashion. Similar results were found in in vitro studies. Conclusion: The protective effect of HuangQi decoction for unilateral ureteral obstruction kidney damage in mice was mediated by downregulating the TGF-beta/Smad signaling pathway. 0 2016 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:1761 / 1774
页数:14
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