Download PDF
Hamostaseologie 2023; 43(04): 271-280
DOI: 10.1055/a-2013-0336
Original Article

Inhibition of MicroRNA-122-5p Relieves Myocardial Ischemia-Reperfusion Injury via SOCS1

Jun Zhang
1   Department of Cardiology, Chengdu First People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Li Fu
1   Department of Cardiology, Chengdu First People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Jing Zhang
1   Department of Cardiology, Chengdu First People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Bo Zhou
1   Department of Cardiology, Chengdu First People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Yanrong Tang
1   Department of Cardiology, Chengdu First People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Zhenzhen Zhang
1   Department of Cardiology, Chengdu First People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Tongqing Gu
2   School of Foreign Languages, Chengdu University of Information Technology, Chengdu, Sichuan, People's Republic of China
› Author Affiliations Funding This study was supported by the National Natural Science Foundation of China (no. 81270220).
› Further Information
Also available at
   Permissions and Reprints

Abstract

Objective Evidence has shown that microRNA (miR)-122–5p is a diagnostic biomarker of acute myocardial infarction. Here, we aimed to uncover the functions of miR-122–5p in the pathological process of myocardial ischemia-reperfusion injury (MI/RI).

Methods An MI/RI model was established by left anterior descending coronary artery ligation in mice. The levels of miR-122–5p, suppressor of cytokine signaling-1 (SOCS1), phosphorylation of Janus kinase 2 (p-JAK2), and signal transducers and activators of transcription (p-STAT3) in the myocardial tissues of mice were measured. Downregulated miR-122–5p or upregulated SOCS1 recombinant adenovirus vectors were injected into mice before MI/RI modeling. The cardiac function, inflammatory response, myocardial infarction area, pathological damage, and cardiomyocyte apoptosis in the myocardial tissues of mice were evaluated. Cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) injury and cardiomyocyte biological function was tested upon transfection of miR-122–5p inhibitor. The target relation between miR-122–5p and SOCS1 was evaluated.

Results miR-122–5p expression and p-JAK2 and p-STAT3 expression were high, and SOCS1 expression was low in the myocardial tissues of MI/RI mice. Decreasing miR-122–5p or increasing SOCS1 expression inactivated the JAK2/STAT3 pathway to alleviate MI/RI by improving cardiac function and reducing inflammatory reaction, myocardial infarction area, pathological damage, and cardiomyocyte apoptosis in mice. Silencing of SOCS1 reversed depleted miR-122–5p-induced cardioprotection for MI/RI mice. In vitro experiments revealed that the downregulation of miR-122–5p induced proliferative, migratory, and invasive capabilities of H/R cardiomyocytes while inhibiting apoptosis. Mechanically, SOCS1 was a target gene of miR-122–5p.

Conclusion Our study summarizes that inhibition of miR-122–5p induces SOCS1 expression, thereby relieving MI/RI in mice.

Keywords

myocardial ischemia reperfusion injury - microRNA-122–5p - suppressor of cytokine signaling-1 - Janus kinase 2/STAT3 - cardiomyocyte - inflammation - cardiac function

Ethical Statement

Experimental approval was signed by the Ethics Committee of Chengdu First People's Hospital. Animal suffering was minimized as much as possible.


Supplementary Material



Publication History

Received: 26 August 2022

Accepted: 11 January 2023

Article published online:
07 March 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M, Eckle T. Myocardial ischemia reperfusion injury: from basic science to clinical bedside. Semin Cardiothorac Vasc Anesth 2012; 16 (03) 123-132
    CrossrefPubMedGoogle Scholar
  • 2 Wan Ab Naim WN, Mohamed Mokhtarudin MJ, Chan BT, Lim E, Ahmad Bakir A, Nik Mohamed NA. The study of myocardial ischemia-reperfusion treatment through computational modelling. J Theor Biol 2021; 509: 110527
    CrossrefPubMedGoogle Scholar
  • 3 Ibáñez B, Heusch G, Ovize M, Van de Werf F. Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 2015; 65 (14) 1454-1471
    CrossrefPubMedGoogle Scholar
  • 4 Ye Y, Perez-Polo JR, Qian J, Birnbaum Y. The role of microRNA in modulating myocardial ischemia-reperfusion injury. Physiol Genomics 2011; 43 (10) 534-542
    CrossrefPubMedGoogle Scholar
  • 5 Singh S, de Ronde MWJ, Kok MGM. et al. MiR-223-3p and miR-122-5p as circulating biomarkers for plaque instability. Open Heart 2020; 7 (01) e001223
    CrossrefPubMedGoogle Scholar
  • 6 Hänninen M, Jäntti T, Tolppanen H. et al; For The CardShock Study Group. Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock. Int J Mol Sci 2020; 21 (21) 7925
    CrossrefPubMedGoogle Scholar
  • 7 Wang Y, Chang W, Zhang Y. et al. Circulating miR-22-5p and miR-122-5p are promising novel biomarkers for diagnosis of acute myocardial infarction. J Cell Physiol 2019; 234 (04) 4778-4786
    CrossrefPubMedGoogle Scholar
  • 8 Liu X, Meng H, Jiang C, Yang S, Cui F, Yang P. Differential microRNA expression and regulation in the rat model of post-infarction heart failure. PLoS One 2016; 11 (08) e0160920
    CrossrefPubMedGoogle Scholar
  • 9 Lin J, Zheng X. Salvianolate blocks apoptosis during myocardial infarction by down regulating miR-122-5p. Curr Neurovasc Res 2017; 14 (04) 323-329
    CrossrefPubMedGoogle Scholar
  • 10 Sano T, Izuishi K, Hossain MA. et al. Protective effect of lipopolysaccharide preconditioning in hepatic ischaemia reperfusion injury. HPB (Oxford) 2010; 12 (08) 538-545
    CrossrefPubMedGoogle Scholar
  • 11 Liu SZ, He XM, Zhang X, Zeng FC, Wang F, Zhou XY. Ischemic preconditioning-induced SOCS-1 protects rat intestinal ischemia reperfusion injury via degradation of TRAF6. Dig Dis Sci 2017; 62 (01) 105-114
    CrossrefPubMedGoogle Scholar
  • 12 Tajiri K, Imanaka-Yoshida K, Matsubara A. et al. Suppressor of cytokine signaling 1 DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis. J Immunol 2012; 189 (04) 2043-2053
    CrossrefPubMedGoogle Scholar
  • 13 Eisenhardt SU, Weiss JB, Smolka C. et al. MicroRNA-155 aggravates ischemia-reperfusion injury by modulation of inflammatory cell recruitment and the respiratory oxidative burst. Basic Res Cardiol 2015; 110 (03) 32
    CrossrefPubMedGoogle Scholar
  • 14 Wang H, Li Z, Gao J, Liao Q. Circular RNA circPTK2 regulates oxygen-glucose deprivation-activated microglia-induced hippocampal neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1β signaling. Int J Biol Macromol 2019; 129: 488-496
    CrossrefPubMedGoogle Scholar
  • 15 Liao Y, Hu X, Guo X, Zhang B, Xu W, Jiang H. Promoting effects of IL–23 on myocardial ischemia and reperfusion are associated with increased expression of IL–17A and upregulation of the JAK2–STAT3 signaling pathway. Mol Med Rep 2017; 16 (06) 9309-9316
    CrossrefPubMedGoogle Scholar
  • 16 Hsu CP, Zhai P, Yamamoto T. et al. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation 2010; 122 (21) 2170-2182
    CrossrefPubMedGoogle Scholar
  • 17 Zheng T, Yang J, Zhang J. et al. Downregulated microRNA-327 attenuates oxidative stress-mediated myocardial ischemia reperfusion injury through regulating the FGF10/Akt/Nrf2 signaling pathway. Front Pharmacol 2021; 12: 669146
    CrossrefPubMedGoogle Scholar
  • 18 Ku HC, Chen WP, Su MJ. DPP4 deficiency preserves cardiac function via GLP-1 signaling in rats subjected to myocardial ischemia/reperfusion. Naunyn Schmiedebergs Arch Pharmacol 2011; 384 (02) 197-207
    CrossrefPubMedGoogle Scholar
  • 19 Dong W, Yang R, Yang J. et al. Resveratrol pretreatment protects rat hearts from ischemia/reperfusion injury partly via a NALP3 inflammasome pathway. Int J Clin Exp Pathol 2015; 8 (08) 8731-8741
    PubMedGoogle Scholar
  • 20 Zhang Y, Li H, Zhao G. et al. Hydrogen sulfide attenuates the recruitment of CD11b+Gr-1+ myeloid cells and regulates Bax/Bcl-2 signaling in myocardial ischemia injury. Sci Rep 2014; 4: 4774
    CrossrefPubMedGoogle Scholar
  • 21 Huang Y, Long X, Li X, Li S, He J. The role of oxymatrine in amelioration of acute lung injury subjected to myocardial I/R by inhibiting endoplasmic reticulum stress in diabetic rats. Evid Based Complement Alternat Med 2020; 2020: 8836904
    CrossrefPubMedGoogle Scholar
  • 22 Zhang J, Shi X, Gao J. et al. Danhong injection and trimetazidine protect cardiomyocytes and enhance calcium handling after myocardial infarction. Evid Based Complement Alternat Med 2021; 2021: 2480465
    PubMedGoogle Scholar
  • 23 Zhang Y, Fan X, Yang H. Long noncoding RNA FTX ameliorates hydrogen peroxide-induced cardiomyocyte injury by regulating the miR-150/KLF13 axis. Open Life Sci 2020; 15 (01) 1000-1012
    CrossrefPubMedGoogle Scholar
  • 24 Shimada BK, Yorichika N, Higa JK. et al. mTOR-mediated calcium transients affect cardiac function in ex vivo ischemia-reperfusion injury. Physiol Rep 2021; 9 (06) e14807
    CrossrefPubMedGoogle Scholar
  • 25 Wu X, Liu Y, Mo S, Wei W, Ye Z, Su Q. LncRNA TUG1 competitively binds to miR-340 to accelerate myocardial ischemia-reperfusion injury. FASEB J 2021; 35 (01) e21163
    PubMedGoogle Scholar
  • 26 Lang Z, Fan X, Lin H, Qiu L, Zhang J, Gao C. Silencing of SNHG6 alleviates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by modulating miR-135a-5p/HIF1AN to activate Shh/Gli1 signalling pathway. J Pharm Pharmacol 2021; 73 (01) 22-31
    CrossrefPubMedGoogle Scholar
  • 27 Diaz D, Prieto A, Reyes E, Barcenilla H, Monserrat J, Alvarez-Mon M. Flow cytometry enumeration of apoptotic cancer cells by apoptotic rate. Methods Mol Biol 2015; 1219: 11-20
    CrossrefPubMedGoogle Scholar
  • 28 Huang Y, Yu S, Cao S. et al. MicroRNA-222 promotes invasion and metastasis of papillary thyroid cancer through targeting protein phosphatase 2 regulatory subunit B alpha expression. Thyroid 2018; 28 (09) 1162-1173
    CrossrefPubMedGoogle Scholar
  • 29 Qiu K, Xie Q, Jiang S, Lin T. Silencing of DJ-1 reduces proliferation, invasion, and migration of papillary thyroid cancer cells in vitro, probably by increase of PTEN expression. Int J Clin Exp Pathol 2019; 12 (06) 2046-2055
    PubMedGoogle Scholar
  • 30 Cortez-Dias N, Costa MC, Carrilho-Ferreira P. et al. Circulating miR-122-5p/miR-133b ratio is a specific early prognostic biomarker in acute myocardial infarction. Circ J 2016; 80 (10) 2183-2191
    CrossrefPubMedGoogle Scholar
  • 31 Peng H, Luo Y, Ying Y. lncRNA XIST attenuates hypoxia-induced H9c2 cardiomyocyte injury by targeting the miR-122-5p/FOXP2 axis. Mol Cell Probes 2020; 50: 101500
    CrossrefPubMedGoogle Scholar
  • 32 Song W, Zhang T, Yang N, Zhang T, Wen R, Liu C. Inhibition of micro RNA miR-122-5p prevents lipopolysaccharide-induced myocardial injury by inhibiting oxidative stress, inflammation and apoptosis via targeting GIT1. Bioengineered 2021; 12 (01) 1902-1915
    CrossrefPubMedGoogle Scholar
  • 33 Yang Z, Wu W, Ou P. et al. MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3. Mol Cell Biochem 2021; 476 (02) 1257-1267
    CrossrefPubMedGoogle Scholar
  • 34 Lu Z, Feng H, Shen X. et al. MiR-122-5p protects against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells. Life Sci 2020; 256: 117851
    CrossrefPubMedGoogle Scholar
  • 35 Yuan W, Liang L, Huang K. et al. MiR-122-5p and miR-326-3p promote cadmium-induced NRK-52E cell apoptosis by downregulating PLD1. Environ Toxicol 2020; 35 (12) 1334-1342
    CrossrefPubMedGoogle Scholar
  • 36 Galam L, Parthasarathy PT, Cho Y. et al. Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection against hyperoxic acute lung injury. Free Radic Biol Med 2015; 84: 196-205
    CrossrefPubMedGoogle Scholar
  • 37 Zhang Y, Shi K, Lin T. et al. Ganoderic acid A alleviates myocardial ischemia-reperfusion injury in rats by regulating JAK2/STAT3/NF-κB pathway. Int Immunopharmacol 2020; 84: 106543
    CrossrefPubMedGoogle Scholar
  • 38 Bai R, Yin X, Feng X. et al. Corydalis hendersonii Hemsl. protects against myocardial injury by attenuating inflammation and fibrosis via NF-κB and JAK2-STAT3 signaling pathways. J Ethnopharmacol 2017; 207: 174-183
    CrossrefPubMedGoogle Scholar