Login Register Cart 0
Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

MicroR-26b Targets High Mobility Group, AT-hook 2 to Ameliorate Myocardial Infarction-induced Fibrosis by Suppression of Cardiac Fibroblasts Activation

Author(s): Xiao Chen, Zhaosheng Ding, Tong Li, Wei Jiang, Jiawei Zhang and Xuejun Deng*

Volume 17, Issue 2, 2020

Page: [204 - 213] Pages: 10

DOI: 10.2174/1567202617666200506101258

Price: $65

Abstract

Background: Myocardial Fibrosis (MF) is an important physiological change after myocardial infarction (MI). MicroRNA-26b (MiR-26b) has a certain inhibitory effect on pulmonary fibrosis. However, the role of miR-26b in MI-induced MF rats and underlying molecular mechanisms remain unknown.

Methods: Forty male Sprague Dawley (SD) rats weighing 200-250 g were divided into four groups (n=10): Sham group, MF group, MF + negative control (NC) agomir group and MF + miR-26b agomir group. Cardiac fibroblasts were isolated from cardiac tissue. Fibrosis levels were detected by MASSON staining, while the expression of related genes was detected by RT-qPCR, Western blotting and Immunohistochemistry, respectively. TargetScan and dual-luciferase reporter assay were utilized to predict the relationship between miR-26b and high mobility group, AT-hook 2 (HMGA2).

Results: The study found the expression of miR-26b to be down-regulated in the myocardium of MF rats (P<0.01). miR-26b overexpression in vitro significantly reduced the survival rate of cardiac fibroblasts and inhibited the expression of the fibrillar-associated protein (α-SMA alphasmooth muscle actin (α-SMA) and collagen I) (P<0.01). TargetScan indicated that HMGA2 was one of the target genes of miR-26b; dual-luciferase reporter assay further confirmed the targeted regulatory relationship (P<0.01). Moreover, miR-26b overexpression significantly reduced the expression of HMGA2 (P<0.01). Notably, HMGA2 overexpression reversed the inhibitory effect of miR-26b overexpression on cardiac fibroblast viability and the expression of α-SMA and collagen I (P<0.01). Animal experiments further indicated that miR-26b overexpression inhibited MIinduced rat MF by inhibiting the expression of HMGA2 (P<0.05, P<0.01).

Conclusion: In short, these findings indicate that miR-26b targets HMGA2 to ameliorate MI-induced fibrosis by suppression of cardiac fibroblasts activation.

Keywords: Myocardial infarction, myocardial fibrosis, mir-26b, high mobility group, AT-hook 2, cardiac fibroblasts.

« Previous
[1]
Minicucci MF, Azevedo PS, Polegato BF, Paiva SA, Zornoff LA. Heart failure after myocardial infarction: Clinical implications and treatment. Clin Cardiol 2011; 34(7): 410-4.
[http://dx.doi.org/10.1002/clc.20922] [PMID: 21688276]
[2]
Zhang X, Hu W, Feng F, Xu J, Wu F. Apelin-13 protects against myocardial infarction-induced myocardial fibrosis. Mol Med Rep 2016; 13(6): 5262-8.
[http://dx.doi.org/10.3892/mmr.2016.5163] [PMID: 27109054]
[3]
Al Hattab D, Czubryt MP. A primer on current progress in cardiac fibrosis. Can J Physiol Pharmacol 2017; 95(10): 1091-9.
[http://dx.doi.org/10.1139/cjpp-2016-0687] [PMID: 28273426]
[4]
Frangogiannis NG. Fibroblasts and the extracellular matrix in right ventricular disease. Cardiovasc Res 2017; 113(12): 1453-64.
[http://dx.doi.org/10.1093/cvr/cvx146] [PMID: 28957531]
[5]
Sun Y, Zhang JQ, Zhang J, Lamparter S. Cardiac remodeling by fibrous tissue after infarction in rats. J Lab Clin Med 2000; 135(4): 316-23.
[http://dx.doi.org/10.1067/mlc.2000.105971] [PMID: 10779047]
[6]
Philip JL, Xu X, Han M, Akhter SA, Razzaque MA. Regulation of cardiac fibroblast-mediated maladaptive ventricular remodeling by beta-arrestins 2019; 14(7): e0219011.
[7]
Wang C, Luo H, Xu Y, Tao L, Chang C, Shen X. Salvianolic acid B-alleviated angiotensin II induces cardiac fibrosis by suppressing NF-κB pathway in vitro. Med Sci Monit 2018; 24: 7654-64.
[http://dx.doi.org/10.12659/MSM.908936] [PMID: 30365482]
[8]
Wu W, Yang J, Feng X, et al. MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells. Mol Cancer 2013; 12: 30.
[http://dx.doi.org/10.1186/1476-4598-12-30] [PMID: 23617834]
[9]
Hu Y, Liu Q, Zhang M, Yan Y, Yu H, Ge L. MicroRNA-362-3p attenuates motor deficit following spinal cord injury via targeting paired box gene 2. J Integr Neurosci 2019; 18(1): 57-64.
[PMID: 31091849]
[10]
Silvestri P, Di Russo C, Rigattieri S, et al. MicroRNAs and ischemic heart disease: towards a better comprehension of pathogenesis, new diagnostic tools and new therapeutic targets. Recent Pat Cardiovasc Drug Discov 2009; 4(2): 109-18.
[http://dx.doi.org/10.2174/157489009788452977] [PMID: 19519553]
[11]
Lima J Jr, Batty JA, Sinclair H, Kunadian V. MicroRNAs in ischemic heart disease: From pathophysiology to potential clinical applications. Cardiol Rev 2017; 25(3): 117-25.
[http://dx.doi.org/10.1097/CRD.0000000000000114] [PMID: 27465537]
[12]
Hong Y, Cao H, Wang Q, Ye J, Sui L, Feng J, et al. MiR-22 may suppress fibrogenesis by targeting TGFbetaR I in cardiac fibroblasts: Cellular physiology and biochemistry. Int J Exper Cell Physiol Biochem Pharmacol 2016; 40(6): 1345-53.
[13]
Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456(7224): 980-4.
[http://dx.doi.org/10.1038/nature07511] [PMID: 19043405 ]
[14]
van Rooij E, Sutherland LB, Thatcher JE, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 2008; 105(35): 13027-32.
[http://dx.doi.org/10.1073/pnas.0805038105] [PMID: 18723672]
[15]
Duisters RF, Tijsen AJ, Schroen B, et al. miR-133 and miR-30 regulate connective tissue growth factor: Implications for a role of microRNAs in myocardial matrix remodeling. Circulat Res 2009; 104(2): 170-8.
[16]
Chen YC, Chen BC, Yu CC, Lin SH, Lin CH. miR-19a, -19b, and -26b mediate CTGF expression and pulmonary fibroblast differentiation. J Cell Physiol 2016; 231(10): 2236-48.
[http://dx.doi.org/10.1002/jcp.25341] [PMID: 26873752]
[17]
Wang YC, Liu JS, Tang HK, et al. miR 221 targets HMGA2 to inhibit bleomycin induced pulmonary fibrosis by regulating TGF β1/Smad3-induced EMT. Int J Mol Med 2016; 38(4): 1208-16.
[http://dx.doi.org/10.3892/ijmm.2016.2705] [PMID: 27513632]
[18]
Wang Y, Le Y, Xue JY, Zheng ZJ, Xue YM. Let-7d miRNA prevents TGF-β1-induced EMT and renal fibrogenesis through regulation of HMGA2 expression. Biochem Biophys Res Commun 2016; 479(4): 676-82.
[http://dx.doi.org/10.1016/j.bbrc.2016.09.154] [PMID: 27693697]
[19]
Qian L, Pan S, Shi L, et al. Downregulation of microRNA-218 is cardioprotective against cardiac fibrosis and cardiac function impairment in myocardial infarction by binding to MITF. Aging (Albany NY) 2019; 11(15): 5368-88.
[http://dx.doi.org/10.18632/aging.102112] [PMID: 31408435]
[20]
Sobhy R, Samir M, Abdelmohsen G, et al. Subtle myocardial dysfunction and fibrosis in children with rheumatic heart disease: Insight from 3D echocardiography, 3D speckle tracking and cardiac magnetic resonance imaging. Pediatr Cardiol 2019; 40(3): 518-25.
[http://dx.doi.org/10.1007/s00246-018-2006-5] [PMID: 30315339]
[21]
Chang YY, Wu YW, Lee JK, et al. Effects of 12 weeks of atorvastatin therapy on myocardial fibrosis and circulating fibrosis biomarkers in statin-naive patients with hypertension with atherosclerosis. J Invest Med 2016; 64(7): 1194-9.
[http://dx.doi.org/10.1136/jim-2016-000092]
[22]
Verjans R, Peters T, Beaumont FJ, et al. MicroRNA-221/222 family counteracts myocardial fibrosis in pressure overload-induced heart failure Hypertension (Dallas, Tex: 1979) 2018; 71(2): 280-8.
[23]
López B, Ravassa S, González A, et al. Myocardial collagen cross-linking is associated with heart failure hospitalization in patients with hypertensive heart failure. J Am Coll Cardiol 2016; 67(3): 251-60.
[http://dx.doi.org/10.1016/j.jacc.2015.10.063] [PMID: 26796388]
[24]
Zhu JN, Chen R, Fu YH, et al. Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on attenuating the acute myocardium infarction-induced myocardial fibrosis in rat. PLoS One 2013; 8(9): e75557.
[http://dx.doi.org/10.1371/journal.pone.0075557] [PMID: 24086569]
[25]
Pan Z, Sun X, Shan H, et al. MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene/transforming growth factor-β1 pathway. Circulation 2012; 126(7): 840-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.094524] [PMID: 22811578]
[26]
Ge ZW, Zhu XL, Wang BC, et al. MicroRNA-26b relieves inflammatory response and myocardial remodeling of mice with myocardial infarction by suppression of MAPK pathway through binding to PTGS2. Int J Cardiol 2019; 280: 152-9.
[http://dx.doi.org/10.1016/j.ijcard.2018.12.077] [PMID: 30679074]
[27]
Wang D, Liu C, Wang Y, et al. Impact of miR-26b on cardiomyocyte differentiation in P19 cells through regulating canonical/noncanonical Wnt signaling. Cell Prolif 2017; 50(6): e12371.
[28]
Icli B, Dorbala P, Feinberg MW. An emerging role for the miR-26 family in cardiovascular disease. Trends Cardiovasc Med 2014; 24(6): 241-8.
[http://dx.doi.org/10.1016/j.tcm.2014.06.003] [PMID: 25066487]
[29]
Yang Y, Akada H, Nath D, Hutchison RE, Mohi G. Loss of Ezh2 cooperates with Jak2V617F in the development of myelofibrosis in a mouse model of myeloproliferative neoplasm. Blood 2016; 127(26): 3410-23.
[http://dx.doi.org/10.1182/blood-2015-11-679431] [PMID: 27081096]
[30]
Liang H, Gu Y, Li T, et al. Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis. Cell Death Dis 2014 2014.5e1238.
[http://dx.doi.org/10.1038/cddis.2014.207] [PMID: 24853416]
[31]
Song X, Liu W, Xie S, et al. All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats. Lab Invest 2013; 93(11): 1219-31.
[http://dx.doi.org/10.1038/labinvest.2013.108] [PMID: 24042439]
[32]
McDaniel K, Huang L, Sato K, et al. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury. J Biol Chem 2017; 292(27): 11336-47.
[http://dx.doi.org/10.1074/jbc.M116.773291] [PMID: 28536261]

Rights & Permissions Print Cite
Article Metrics
14
© 2024 Bentham Science Publishers | Privacy Policy