Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (13): 2054-2060.doi: 10.12307/2024.133

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Hypoxic postconditioning protects myocardium by regulating autophagy in aging cardiomyocytes through piRNA-005854

Chi Hongyang1, 2, Yang Huixia1, 2, Hao Yinju3, Yang Anning2, 4, Bai Zhigang2, 5, Jiao Yun2, 6, Xiong Jiantuan2, 4, Ma Shengchao2, 4, Jiang Yideng2, 4   

  1. 1School of Clinical Medicine, 2National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research, 3School of Pharmacy, 4School of Basic Medicine, 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; 6Department of Infection, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2023-01-28 Accepted:2023-04-07 Online:2024-05-08 Published:2023-08-28
  • Contact: Jiang Yideng, MD, Professor, Doctoral supervisor, National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research; School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China Ma Shengchao, MD, Associate professor, Master’s supervisor, National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research; School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Chi Hongyang, Master candidate, School of Clinical Medicine; National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Supported by:
    Key Project of Key Research and Development Program of Ningxia Hui Autonomous Region, No. 2022BFH02013 (to HYJ); Key Project of Key Research and Development Program of Ningxia Hui Autonomous Region, No. 2020BFH02003 (to YAN); Key Project of Key Research and Development Program of Ningxia Hui Autonomous Region, No. 2021BEG02033 (to XJT); Key Project of Key Research and Development Program of Ningxia Hui Autonomous Region, No. 2020BEG03005 (to JY); Key Project of Key Research and Development Program of Ningxia Hui Autonomous Region, No. 2020BFH02001 (to BZG); National Natural Science Foundation of China, No. U21A20343 (to JYD); National Natural Science Foundation of China, No. 82160049 (to XJT); National Natural Science Foundation of China, No. 81900273 (to MSC); National Natural Science Foundation of China, No. 82060412 (to JY); Fundamental Research Funds for Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences, No. 2019PT330002 (to JYD)

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Abstract: BACKGROUND: Ischemic postconditioning is one of the effective ways to reduce ischemia-reperfusion injury and has been more and more widely used in clinical practice in recent years, but its specific molecular mechanism has yet to be studied.  
OBJECTIVE: To investigate the role and mechanism of piRNA-005854 in the aging cardiomyocytes caused by hypoxic postconditioning.
METHODS: In vitro, cardiomyocytes were administered 8 mg/mL D-galactose for 9 days to induce their aging. β-Galactosidase staining was used to observe the aging of cardiomyocytes. Senescent cells were treated with hypoxia/reoxygenation and hypoxic postconditioning. ELISA was utilized to detect changes in myocardial injury markers creatine kinase isoenzyme MB and lactate dehydrogenase levels. Western blot assay was applied to detect the expression changes of autophagy-related proteins LC3II, p62, ULK1 and phosphorylated ULK1 in aging cardiomyocytes. qRT-PCR was employed to determine the expression level of piRNA-005854. piRNA-005854 inhibitor and piRNA-005854 mimics were transferred into aging cardiomyocytes and followed with hypoxic postconditioning. Western blot assay was used to examine the expression of LC3II, p62, ULK1 and phosphorylated ULK1.  
RESULTS AND CONCLUSION: (1) D-galactose induced obvious senescence of cardiomyocytes 9 days later. (2) Compared with the normoxia group, creatine kinase isoenzyme MB and lactate dehydrogenase levels increased in the hypoxia/reoxygenation group (P < 0.01); LC3 II/I expression was increased; p62 expression was decreased; ULK1 phosphorylation level was increased, and piRNA-005854 expression was increased (P < 0.01). (3) Compared with the hypoxia/reoxygenation group, creatine kinase isoenzyme MB and lactate dehydrogenase levels significantly reduced in the hypoxic postconditioning group (P < 0.01); LC3 II/I expression significantly decreased (P < 0.05); p62 expression increased (P < 0.01); ULK1 phosphorylation level decreased (P < 0.05), and piRNA-005854 expression decreased (P < 0.01). (4) After transfection of piRNA-005854 inhibitor, LC3II/I expression was decreased (P < 0.01); the expression of p62 was increased significantly (P < 0.05); the phosphorylation level of ULK1 was decreased significantly (P < 0.01). After transfection of piRNA-005854 mimics, LC3II/I expression was increased significantly; the expression of p62 was decreased, and the phosphorylation level of ULK1 was increased significantly (P < 0.01). (5) The results show that piRNA-005854-mediated reduction of ULK1-dependent autophagy level is a possible mechanism that hypoxic postconditioning exerts its protective effect on aging cardiomyocytes.

Key words: piRNA, autophagy, aging cardiomyocyte, ischemia-reperfusion injury, hypoxia/reoxygenation, hypoxic postconditioning

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