Abstract |
We previously found that hypoxia induced renal tubular epithelial cells (RTECs) release functional extracellular vesicles (EVs), which mediate the protection of remote ischaemic preconditioning (RIPC) for kidney ischaemia-reperfusion (I/R) injury. We intend to investigate whether the EVs were regulated by hypoxia-inducible factor 1α (HIF-1α) and Rab22 during RIPC. We also attempted to determine the potentially protective cargo of the EVs and reveal their underlying mechanism. Hypoxia preconditioning (HPC) of human kidney 2 (HK2) cells was conducted at 1% oxygen (O2) for different amounts of time to simulate IPC in vitro. EVs were isolated and then quantified. HIF-1α- and Rab22-inhibited HK2 cells were used to investigate the role of the HIF-1α/Rab22 pathway in HPC-induced EV production. Both normoxic and HPC EVs were treated in vivo to assess the protective effect of I/R injury. Moreover, microRNA ( miRNA) sequencing analysis and bioinformatics analysis was performed. We revealed that the optimal conditions for simulating IPC in vitro was no more than 12 h under the 1% O2 culture circumstance. HPC enhanced the production of EVs, and the production of EVs was regulated by the HIF-1α/Rab22 pathway during HPC. Moreover, HPC EVs were found to be more effective at attenuating mice renal I/R injury. Furthermore, 16 miRNAs were upregulated in HPC EVs. Functional and pathway analysis indicated that the miRNAs may participate in multiple processes and pathways by binding their targets to influence the biochemical results during RIPC. We demonstrated that HIF-1α/Rab22 pathway mediated RTEC-derived EVs during RIPC. The HPC EVs protected renal I/R injury potentially through differentially expressed miRNAs. Further study is needed to verify the effective EV- miRNAs and their underlying mechanism.
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Authors | Lei Zhang, Han Liu, Kai Xu, Zhixin Ling, Yeqing Huang, Qiang Hu, Kai Lu, Chunhui Liu, Yiduo Wang, Ning Liu, Xiaowen Zhang, Bin Xu, Jianping Wu, Shuqiu Chen, Guangyuan Zhang, Ming Chen |
Journal | International journal of biological sciences
(Int J Biol Sci)
Vol. 15
Issue 6
Pg. 1161-1176
( 2019)
ISSN: 1449-2288 [Electronic] Australia |
PMID | 31223277
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- Hif1a protein, mouse
- Hypoxia-Inducible Factor 1, alpha Subunit
- MicroRNAs
- RNA-Binding Proteins
- Rad51ap1 protein, mouse
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Topics |
- Animals
- Cell Hypoxia
- Cell Line
- DNA-Binding Proteins
(metabolism, physiology)
- Epithelial Cells
(cytology)
- Extracellular Vesicles
(physiology)
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism, physiology)
- Male
- Mice
- Mice, Inbred C57BL
- MicroRNAs
(chemistry, metabolism)
- RNA-Binding Proteins
(metabolism, physiology)
- Reperfusion Injury
(pathology)
- Sequence Analysis, RNA
- Signal Transduction
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