Int J Biol Sci 2021; 17(8):2099-2111. doi:10.7150/ijbs.58163

Research Paper

MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

Jing Ke1,2, Fan Zhao1, Yanwen Luo1, Fangjing Deng1, Xiongfei Wu1✉

1. Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
2. Department of Endocrinology, Ezhou Central Hospital, Ezhou, Hubei, China.

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Citation:
Ke J, Zhao F, Luo Y, Deng F, Wu X. MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway. Int J Biol Sci 2021; 17(8):2099-2111. doi:10.7150/ijbs.58163. Available from https://www.ijbs.com/v17p2099.htm

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Abstract

Renal ischemia-reperfusion injury (IRI) is one of the underlying causes of acute kidney injury and also an unavoidable problem in renal transplantation. Lots of miRNAs and targets have been found to participate in some post-transcriptional processes in renal IRI, however, the detailed knowledge of miRNA targets and mechanism is unknown. In this study, miR-124 was found inhibited and PARP1 was overexpressed in renal IRI cells and mouse models. Dual-luciferase reporter assay revealed that miR-124 post-transcriptionally regulated PAPR1 3′UTR activity. Our results also demonstrated miR-124 negatively regulated PARP1 which played a role in necroptosis of renal ischemia-reperfusion injury by activating TNFα. TNFα induced the RIP1/RIP3 necroptosis signaling pathway to aggravate the renal injury. Collectively, these studies identified PARP1 as a direct target of miR-124 and activated RIP1/RIP3 necroptosis signaling pathway through TNFα. It elucidated the protective effect of miR-124 in renal ischemia-reperfusion injury, which demonstrated the regulatory mechanism of miR-124/PARP1 in renal injury and exhibited the potential as a novel therapeutic for the treatment of renal IRI.

Keywords: MiR-124, PARP1, TNFα/RIP1/RIP3 pathway, renal ischemia-reperfusion injury.