Berberine Protects Glomerular Podocytes via Inhibiting Drp1-Mediated Mitochondrial Fission and Dysfunction

被引:182
作者
Qin, Xin [1 ]
Zhao, Yan [2 ]
Gong, Jing [2 ]
Huang, Wenya [2 ]
Su, Hao [1 ]
Yuan, Fen [1 ]
Fang, Ke [2 ]
Wang, Dingkun [2 ]
Li, Jingbin [2 ]
Zou, Xin [1 ]
Xu, Lijun [1 ]
Dong, Hui [1 ]
Lu, Fuer [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Integrated Tradit Chinese & Western Med, Wuhan, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Integrated Tradit Chinese & Western Med, Tongji Med Coll, Wuhan, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
diabetic kidney disease; podocyte; mitochondrial fission; dynamin-related protein 1; Berberine; DIABETIC-NEPHROPATHY; OXIDATIVE STRESS; SKELETAL-MUSCLE; MESANGIAL CELLS; KIDNEY-DISEASE; APOPTOSIS; INJURY; PLANT; MODULATION; ACTIVATION;
D O I
10.7150/thno.30640
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However, the mechanisms by which FFA leads to mitochondrial damage in glomerular podocytes of DKD and the effects of Berberine (BBR) on podocytes are not fully understood. Methods: Using the db/db diabetic mice model and cultured mouse podocytes, we investigated the molecular mechanism of FFA-induced disturbance of mitochondrial dynamics in podocytes and testified the effects of BBR on regulating mitochondrial dysfunction, podocyte apoptosis and glomerulopathy in the progression of DKD. Results: Intragastric administration of BBR for 8 weeks in db/db mice significantly reversed glucose and lipid metabolism disorders, podocyte damage, basement membrane thickening, mesangial expansion and glomerulosclerosis. BBR strongly inhibited podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation and dysfunction both in vivo and in vitro. Mechanistically, BBR could stabilize mitochondrial morphology in podocytes via abolishing palmitic acid (PA)-induced activation of dynamin-related protein 1 (Drp1). Conclusions: Our study demonstrated for the first time that BBR may have a previously unrecognized role in protecting glomerulus and podocytes via positively regulating Drp1-mediated mitochondrial dynamics. It might serve as a novel therapeutic drug for the treatment of DKD.
引用
收藏
页码:1698 / 1713
页数:16
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