Role of LncRNA MALAT1 in myocardial autophagy reduction in aging rats after ischemic postconditioning

doi:10.12307/2023.478

Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (20): 3173-3179.doi: 10.12307/2023.478

Role of LncRNA MALAT1 in myocardial autophagy reduction in aging rats after ischemic postconditioning

Yang Huixia1, 3, Jie Yuzhen1, 3, Bai Zhigang3, 5, Jiao Yun3, 4, Yang Yong3, 5, Ma Tianlong2, 3, Ma Shengchao2, 3, Jiang Yideng2, 3

1Clinical Medical College, 2Basic Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 4Department of Infection, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 5People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750004, Ningxia Hui Autonomous Region, China

Received:2022-06-24 Accepted:2022-08-08 Online:2023-07-18 Published:2022-11-19
Contact: Jiang Yideng, MD, Professor, Basic Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China Ma Shengchao, MD, Associate professor, Basic Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China
About author:Yang Huixia, Master candidate, Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Supported by:
the National Natural Science Foundation of China, Nos. 81900273 (to MSC) and 81860044 (to YY); Ningxia Hui Autonomous Region Key R&D Programs, Nos. 2020BFH02001 (to BZG) and 2020BEG03005 (to JY)

Abstract

Abstract: BACKGROUND: Ischemic postconditioning can alleviate myocardial ischemia-reperfusion injury, but the specific mechanism is not clear.
OBJECTIVE: To investigate the mechanism of long non-coding RNA (lncRNA) MALAT1 in the reduction of autophagy levels in aging myocardium induced by ischemic postconditioning.
METHODS: Twenty-seven Sprague-Dawley rats aged 22-24 months were randomly divided into three groups, with nine rats in each group: sham operation, ischemia-reperfusion, and ischemic postconditioning groups. Morphological changes of myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. Rat myocardial cells (H9C2) were induced in vitro with 8 mg/mL D-galactose for 9 days and then divided into normoxia, hypoxia-reoxygenation, and hypoxia postconditioning groups. Western blot was used to detect the protein expression levels of LC3II/I and p62. Fluorescence quantitative PCR was used to detect the expression of lncRNA MALAT1 in aging myocardium and aging cardiomyocytes. Autophagy double-labeled adenovirus (RFP-GFP-LC3) was used to observe the changes of autophagic flux in aging cardiomyocytes. lncRNA MALAT1 interference fragment and overexpression plasmid were transfected into aging cardiomyocytes and the protein expression levels of LC3II/I and p62 were detected by western blot.
RESULTS AND CONCLUSION: Compared with the ischemia-reperfusion group, the myocardial tissue structure of the ischemic postconditioning group was basically clear, the nucleus was intact, and the deposition of blue collagen fibers in the myocardial tissue was reduced. Compared with the ischemia-reperfusion group, the expression of LC3II/I was decreased and the expression of p62 was increased in the ischemic postconditioning group (P < 0.05). Compared with the hypoxia-reperfusion group, the expression of LC3II/I was decreased (P < 0.01) and the expression of p62 was increased (P < 0.05) in the hypoxia postconditioning group, and the number of intracellular autophagosomes and autophagolysosomes was decreased (P < 0.05). Compared with the ischemia-reperfusion group, the expression of MALAT1 in the aging myocardial tissue was decreased the ischemic postconditioning group (P < 0.01); compared with the hypoxia-reperfusion group, the expression of MALAT1 in aging cardiomyocytes was decreased in the hypoxic postconditioning group (P < 0.01). Compared with the hypoxia postconditioning+si-NC group, the expression of LC3II/I was decreased and the expression of p62 was increased in the hypoxia postconditioning +si-lncRNA MALAT1 (P < 0.01); compared with the hypoxia postconditioning+ad-NC group, the expression of LC3II/I was increased and the expression of p62 was decreased in the hypoxia postconditioning+ad-lncRNA MALAT1 group (P < 0.01). To conclude, the lncRNA MALAT1 mediated reduction of autophagy levels is an important mechanism underlying the protective effect of ischemic postconditioning in aging myocardium.

Key words: long non-coding RNA MALAT1, ischemia-reperfusion injury, ischemic postconditioning, aging H9C2 cells, autophagy

CLC Number:

Yang Huixia, Jie Yuzhen, Bai Zhigang, Jiao Yun, Yang Yong, Ma Tianlong, Ma Shengchao, Jiang Yideng. Role of LncRNA MALAT1 in myocardial autophagy reduction in aging rats after ischemic postconditioning[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(20): 3173-3179.

Figures/Tables 7

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Role of LncRNA MALAT1 in myocardial autophagy reduction in aging rats after ischemic postconditioning

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