Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys.
Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys.
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肌因子介导的肌肉-肾脏串扰抑制受损肾脏的代谢重编程和纤维化
DOI：
10.1038/s41467-017-01646-6
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发表时间：
2017-11-14
影响因子：
16.6
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Peng H;Wang Q;Lou T;Qin J;Jung S;Shetty V;Li F;Wang Y;Feng XH;Mitch WE;Graham BH;Hu Z
肾损伤启动肾小管细胞的代谢重编程，导致慢性肾病（CKD）的发展。运动与CKD患者的有益效果相关。在这里，我们表明，诱导肌因子，鸢尾素，改善肾脏能量代谢，防止肾损伤。在对肾损伤的反应中，肌肉特异性PGC-1α过表达（mPGC-1α）的小鼠表现出肾损伤和纤维化减轻。代谢组学分析显示mPGC-1α小鼠受损肾脏中ATP产生增加和能量代谢改善。我们确定鸢尾素是一种血清因子，在进行性肾损伤期间通过抑制TGF-β 1型受体介导这些代谢作用。从血清中去除鸢尾素减弱了在mPGC-1α血清处理的肾小管细胞中观察到的耗氧率诱导。在小鼠中，重组鸢尾素给药减轻肾损伤和纤维化，并改善肾功能。我们认为，肌因子介导的肌肉-肾脏串扰可以抑制肾脏疾病期间的代谢重编程和纤维化。
Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Exercise has been associated with beneficial effects in patients with CKD. Here we show that the induction of a myokine, irisin, improves kidney energy metabolism and prevents kidney damage. In response to kidney injury, mice with muscle-specific PGC-1α overexpression (mPGC-1α) exhibit reduced kidney damage and fibrosis. Metabolomics analysis reveals increased ATP production and improved energy metabolism in injured kidneys from mPGC-1α mice. We identify irisin as a serum factor that mediates these metabolic effects during progressive kidney injury by inhibiting TGF-β type 1 receptor. Irisin depletion from serum blunts the induction of oxygen consumption rate observed in tubule cells treated with mPGC-1α serum. In mice, recombinant irisin administration attenuates kidney damage and fibrosis and improves kidney functions. We suggest that myokine-mediated muscle-kidney crosstalk can suppress metabolic reprograming and fibrogenesis during kidney disease.
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运动和PGC1alpha在炎症和慢性疾病中的作用。
影响因子：
64.8
作者：
Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
7.3
作者：
Lin, Jamie S.;Shi, Yuanyuan;Peng, Hui;Shen, Xiaojie;Thomas, Sandhya;Wang, Yanlin;Truong, Luan D.;Dryer, Stuart E.;Hu, Zhaoyong;Xu, Jing
通讯作者：
Xu, Jing
影响因子：
19.6
作者：
Ma, LJ;Fogo, AB
通讯作者：
Fogo, AB
CKD 通过 Rho 相关蛋白激酶 1 激活刺激肌肉蛋白损失
影响因子：
13.6
作者：
Peng, Hui;Cao, Jin;Hu, Zhaoyong
通讯作者：
Hu, Zhaoyong
DOI：
10.1053/j.ajkd.2008.07.034
发表时间：
2009-02
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Snyder JJ;Foley RN;Collins AJ
通讯作者：
Collins AJ