AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury

Wugang Zhou; Lv Ji; Xuqin Liu; Dan Tu; Ningning Shi; Wangmu Yangqu; Shi Chen; Pingjin Gao; Hong Zhu; Chengchao Ruan

Biomedical Journal (Dec 2022)

AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury

Wugang Zhou,
Lv Ji,
Xuqin Liu,
Dan Tu,
Ningning Shi,
Wangmu Yangqu,
Shi Chen,
Pingjin Gao,
Hong Zhu,
Chengchao Ruan

Affiliations

Wugang Zhou: Department of Emergency, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China
Lv Ji: Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China
Xuqin Liu: Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China
Dan Tu: Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China
Ningning Shi: Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China
Wangmu Yangqu: Department of Intensive Care Unit, Shigatse People's Hospital, Shigatse, Tibet Autonomous Region, China
Shi Chen: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China; Brain Center, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
Pingjin Gao: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Hong Zhu: Clinical Medical School, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Corresponding author. Clinical Medical School, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Room 401, Building 1, Jinzun Rd. 115, Pudong Dist., Shanghai 200125, China.
Chengchao Ruan: State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Corresponding author. Department of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin 2nd Rd. 197, Shanghai 200024, China.

Journal volume & issue: Vol. 45, no. 6
pp. 870 – 882

Abstract

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Background: Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction. The role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury remains unclear. This study was aimed at probing into the role and the underlying regulatory mechanism of AIFM1 in myocardial injury. Methods: H9c2 cardiomyocytes and C57BL/6 mice were used for myocardial hypoxic/ischemic injury and myocardial infarction animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of AIFM1 mRNA and miR-145-5p. Western blot was used for examining the expression levels of AIFM1, caspase-3, cleaved caspase-3, p-53, and γ-H2AX. Cell viability was examined by cell counting kit-8 (CCK-8) assay and BrdU assay. Interaction between AIFM1 and miR-145-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. Results: AIFM1 expression was markedly highly elevated, while miR-145-5p expression was significantly down-regulated in the myocardial infarction animal model and H9c2 cells under hypoxia. Augmentation of AIFM1 led to a dramatic decrease of cell viability, accompanied by an increase of the secretion of the inflammatory cytokines IL-1β, TNF-α, IL-6, and the expression of cleaved caspase-3. Furthermore, AIFM1 was identified as a target of miR-145-5p. In addition, miR-145-5p/AIFM1 axis regulated the expression of p53. Conclusion: AIFM1 may exacerbate myocardial ischemic injury by promoting inflammation and the injury of cardiomyocytes, and its up-regulation may be partly due to the down-regulation of miR-145-5p.

Published in Biomedical Journal

ISSN: 2319-4170 (Print); 2320-2890 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.sciencedirect.com/journal/biomedical-journal

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