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  2. MiR-23a-5p exacerbates intestinal ischemia-reperfusion injury by promoting oxidative stress via targeting PPAR alpha

MiR-23a-5p exacerbates intestinal ischemia-reperfusion injury by promoting oxidative stress via targeting PPAR alpha

  • Biochem Pharmacol. 2020 Oct;180:114194. doi: 10.1016/j.bcp.2020.114194.
L X Li 1 L-H Yin 1 M Gao 1 L-N Xu 1 Y Qi 1 J-Y Peng 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Analysis, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
  • 2 Department of Pharmaceutical Analysis, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China; Key Laboratory for Basic and Applied Research on Pharmacodynamic Substances of Traditional Chinese Medicine of Liaoning Province, Dalian Medical University, Dalian, China; National-Local Joint Engineering Research Center for Drug Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China. Electronic address: jinyongpeng2016@dmu.edu.cn.
Abstract

MiR-23a-5p is involved in the occurrence and development of some serious diseases, but its effects on intestinal ischemia-reperfusion (II/R) injury is unclear. In this research, the hypoxia/reoxygenation (H/R) model on IEC-6 cells and II/R model in mice were used. The data showed that the ROS level in model group was significantly increased compared with control group. The level of intestinal MPO was increased and serum SOD was decreased in mice compared with sham group. Moreover, the expression levels of miR-23a-5p in model groups were obviously increased in vitro and in vivo, while the expression levels of PPARα, FOXO3α, PGC-1α, Nrf2, CAT, NQO1, HO-1 and SOD2 were significantly decreased. The double luciferase reporter gene assay showed that there was binding site between miR-23a-5p and PPARα. When miR-23a-5p was inhibited or PPARα gene was overexpressed, H/R-caused cell damage was alleviated and ROS level was decreased compared with NC group. PPARα expression level was increased, accompanied by the increased levels of FOXO3α, PGC-1α, Nrf2, CAT, NQO1, HO-1 and SOD2. After enhancing miR-23a-5p expression or silencing PPARα gene, H/R-caused cell damage was further aggravated compared with NC group, and ROS level was increased associated with the decreased levels of FOXO3α, PGC-1α, Nrf2, CAT, NQO1, HO-1 and SOD2. Our study demonstrated that miR-23a-5p exacerbated II/R injury by promoting oxidative stress via targeting PPARα, which should be considered as one new drug target to treat II/R injury.

Keywords

Drug target; Intestinal ischemia–reperfusion injury; Oxidative stress; miR-23a-5p/PPARα signal.

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