HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells

微泡 外体 细胞生物学 分泌物 缺氧(环境) 基因敲除 生物 细胞凋亡 化学 内分泌学 小RNA 生物化学 基因 有机化学 氧气
作者
Wei Zhang,Xiangjun Zhou,Qisheng Yao,Yutao Liu,Hao Zhang,Zheng Dong
出处
期刊:American Journal of Physiology-renal Physiology [American Physiological Society]
卷期号:313 (4): F906-F913 被引量:126
标识
DOI:10.1152/ajprenal.00178.2017
摘要

Exosomes are nano-sized vesicles produced and secreted by cells to mediate intercellular communication. The production and function of exosomes in kidney tissues and cells remain largely unclear. Hypoxia is a common pathophysiological condition in kidneys. This study was designed to characterize exosome production during hypoxia of rat renal proximal tubular cells (RPTCs), investigate the regulation by hypoxia-inducible factor-1 (HIF-1), and determine the effect of the exosomes on ATP-depletion-induced tubular cell injury. Hypoxia did not change the average sizes of exosomes secreted by RPTCs, but it significantly increased exosome production in a time-dependent manner. HIF-1 induction with dimethyloxalylglycine also promoted exosome secretion, whereas pharmacological and genetic suppression of HIF-1 abrogated the increase of exosome secretion under hypoxia. The exosomes from hypoxic RPTCs had inhibitory effects on apoptosis of RPTCs following ATP depletion. The protective effects were lost in the exosomes from HIF-1α knockdown cells. It is concluded that hypoxia stimulates exosome production and secretion in renal tubular cells. The exosomes from hypoxic cells are protective against renal tubular cell injury. HIF-1 mediates exosome production during hypoxia and contributes to the cytoprotective effect of the exosomes.
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