Activation of TRPV1 channel antagonizes diabetic nephropathy through inhibiting endoplasmic reticulum-mitochondria contact in podocytes
Activation of TRPV1 channel antagonizes diabetic nephropathy through inhibiting endoplasmic reticulum-mitochondria contact in podocytes
复制标题
TRPV1通道激活通过抑制足细胞内质网-线粒体接触对抗糖尿病肾病
DOI：
10.1016/j.metabol.2020.154182
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发表时间：
2020
影响因子：
9.8
通讯作者：
Zhu Zhiming
中科院分区：
文献类型：
--
作者：
Wei Xiao;Wei Xing;Lu Zongshi;Li Li;Hu Yingru;Sun Fang;Jiang Yanli;Ma Huan;Zheng Hongting;Yang Gangyi;Liu Daoyan;Gao Peng;Zhu Zhiming
The impairment of podocyte protein filtration function caused by excessive mitochondrial calcium intake is a critical feature of diabetic nephropathy (DN). Ca2+channel transient receptor potential cation channel subfamily V member 1 (TRPV1) has been reported to protect against ischemia-reperfusion induced acute renal injury, but there is no report about its role in DN. Here, we report that dietary capsaicin potently inhibits and reverses chronic renal structural and functional damages in db/db or streptozotocin (STZ)-induced diabetic mice in a TRPV1-dependent manner. Activation of TRPV1 by capsaicin alleviated hyperglycemia-induced mitochondrial dysfunction in podocytes, accompanied by reduced mitochondria-associated membranes (MAMs) formation and fewer Ca2+transport from endoplasmic reticulum (ER) to mitochondria. Mechanistically, TRPV1-mediated transient Ca2+influx activated 5′ AMP-activated protein kinase (AMPK) that reduced the transcription of Fundc1, a key molecule participating in MAMs formation. Inhibition of AMPK or overexpression of Fundc1 obviously blocked the inhibitory effect of capsaicin on MAMs formation and functional decline in podocytes. These findings emphasize the critical role of mitochondrial Ca2+homeostasis in the maintenance of normal renal function and suggest an effective intervention method to counteract DN.
