PMID- 28679592 OWN - NLM STAT- MEDLINE DCOM- 20171019 LR - 20200725 IS - 1522-1466 (Electronic) IS - 1931-857X (Print) IS - 1522-1466 (Linking) VI - 313 IP - 4 DP - 2017 Oct 1 TI - HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells. PG - F906-F913 LID - 10.1152/ajprenal.00178.2017 [doi] AB - 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-1alpha 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. CI - Copyright (c) 2017 the American Physiological Society. FAU - Zhang, Wei AU - Zhang W AD - Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China. AD - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia; and. FAU - Zhou, Xiangjun AU - Zhou X AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China. AD - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia; and. FAU - Yao, Qisheng AU - Yao Q AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Liu, Yutao AU - Liu Y AD - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia; and. FAU - Zhang, Hao AU - Zhang H AD - Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China. FAU - Dong, Zheng AU - Dong Z AD - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia; and. AD - Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, China. LA - eng GR - I01 BX000319/BX/BLRD VA/United States GR - R01 DK087843/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20170705 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Amino Acids, Dicarboxylic) RN - 0 (Hypoxia-Inducible Factor 1) RN - VVW38EB8YS (oxalylglycine) SB - IM MH - Amino Acids, Dicarboxylic MH - Animals MH - Cell Line MH - Exosomes/*metabolism MH - Hypoxia/*physiopathology MH - Hypoxia-Inducible Factor 1/*physiology MH - Kidney Tubules, Proximal/*metabolism MH - Mice PMC - PMC5668579 OTO - NOTNLM OT - ATP depletion OT - HIF-1 OT - exosome OT - hypoxia OT - kidney injury EDAT- 2017/07/07 06:00 MHDA- 2017/10/20 06:00 PMCR- 2018/10/01 CRDT- 2017/07/07 06:00 PHST- 2017/04/04 00:00 [received] PHST- 2017/06/21 00:00 [revised] PHST- 2017/06/26 00:00 [accepted] PHST- 2017/07/07 06:00 [pubmed] PHST- 2017/10/20 06:00 [medline] PHST- 2017/07/07 06:00 [entrez] PHST- 2018/10/01 00:00 [pmc-release] AID - ajprenal.00178.2017 [pii] AID - F-00178-2017 [pii] AID - 10.1152/ajprenal.00178.2017 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F906-F913. doi: 10.1152/ajprenal.00178.2017. Epub 2017 Jul 5.