Zhang Wei, Zhou Xiangjun, Yao Qisheng, Liu Yutao, Zhang Hao, Dong Zheng
Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China.
Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia; and.
Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F906-F913. doi: 10.1152/ajprenal.00178.2017. Epub 2017 Jul 5.
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.
外泌体是细胞产生并分泌的纳米级囊泡，用于介导细胞间通讯。外泌体在肾组织和细胞中的产生及功能仍 largely 不清楚。缺氧是肾脏中常见的病理生理状况。本研究旨在表征大鼠肾近端小管细胞（RPTCs）缺氧期间外泌体的产生，研究缺氧诱导因子-1（HIF-1）的调节作用，并确定外泌体对ATP耗竭诱导的肾小管细胞损伤的影响。缺氧并未改变RPTCs分泌的外泌体的平均大小，但以时间依赖性方式显著增加了外泌体的产生。用二甲基草酰甘氨酸诱导HIF-1也促进了外泌体分泌，而HIF-1的药理学和基因抑制消除了缺氧条件下外泌体分泌的增加。缺氧RPTCs产生的外泌体对ATP耗竭后RPTCs的凋亡具有抑制作用。来自HIF-1α敲低细胞的外泌体失去了保护作用。结论是缺氧刺激肾小管细胞中外泌体的产生和分泌。缺氧细胞产生的外泌体对肾小管细胞损伤具有保护作用。HIF-1在缺氧期间介导外泌体的产生，并有助于外泌体的细胞保护作用。
