Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling

被引：145

作者：

Xie, Xi ^{[1
,2
]}

Chang, Xiuting ^{[1
]}

Chen, Lei ^{[3
]}

Huang, Kaipeng ^{[1
]}

Huang, Juan ^{[1
]}

Wang, Shaogui ^{[1
]}

Shen, Xiaoyan ^{[1
]}

Liu, Peiqing ^{[1
]}

Huang, Heqing ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China

[2] Hainan Univ, Dept Pharmaceut Engn, Ocean Coll, Haikou 570228, Peoples R China

[3] Sun Yat Sen Univ, Sch Pharmaceut Sci, New Drug Res & Dev Ctr, Guangzhou 510006, Guangdong, Peoples R China

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2013年 / 381卷 / 1-2期

基金：

中国国家自然科学基金;

关键词：

Diabetic nephropathy; Berberine; RhoA/ROCK; NF-kappa B; Fibronectin; RHO-KINASE INHIBITOR; KAPPA-B ACTIVATION; MESANGIAL CELLS; MATRIX ACCUMULATION; OXIDATIVE STRESS; GENE-EXPRESSION; NEPHROPATHY; RESISTANT; KIDNEY; PROLIFERATION;

D O I：

10.1016/j.mce.2013.07.019

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The accumulation of glomerular extracellular matrix proteins, especially fibronectin (FN), is a critical pathological characteristic of diabetic renal fibrosis. Inflammation mediated by nuclear factor-kappa B (NF-kappa B) plays a critical role in the pathogenesis of diabetic nephropathy (DN). RhoA/ROCK signaling is responsible for FN accumulation and NF-kappa B activation. Berberine (BBR) treatment significantly inhibited renal inflammation and thus improved renal damage in diabetes. Here, we study whether BBR inhibits FN accumulation and NF-kappa B activation by inhibiting RhoA/ROCK signaling and the underlying mechanisms involved. Results showed that BBR effectively inhibited RhoA/ROCK signaling activation in diabetic rat kidneys and high glucose-induced glomerular mesangial cells (GMCs) and simultaneously down-regulated NF-kappa B activity, which was accompanied by reduced intercellular adhesionmolecule-1, transforming growth factor-beta 1 and FN overproduction. Furthermore, we observed that BBR abrogated high glucose-mediated reactive oxygen species generation in GMCs. BBR and N-acetylcysteine inhibited RhoA/ROCK signaling activation in high glucose-exposed GMCs. Collectively, our data suggest that the renoprotective effect of BBR on DN partly depends on RhoA/ROCK inhibition. The anti-oxidative stress effect of BBR is responsible for RhoA/ROCK inhibition in DN. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：56 / 65

页数：10

共 42 条

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