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

[ Vol. 17 , Issue. 2 ]

Author(s):

Xiao Chen, Zhaosheng Ding, Tong Li, Wei Jiang, Jiawei Zhang and Xuejun Deng*   Pages 204 - 213 ( 10 )

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.

Affiliation:

Department of Cardiopulmonary Rehabilitation, Jiangsu Rongjun Hospital, Wuxi City, Jiangsu Province, 214000, Department of Cardiopulmonary Rehabilitation, Jiangsu Rongjun Hospital, Wuxi City, Jiangsu Province, 214000, Department of Cardiopulmonary Rehabilitation, Jiangsu Rongjun Hospital, Wuxi City, Jiangsu Province, 214000, Department of Cardiopulmonary Rehabilitation, Jiangsu Rongjun Hospital, Wuxi City, Jiangsu Province, 214000, Department of Cardiopulmonary Rehabilitation, Jiangsu Rongjun Hospital, Wuxi City, Jiangsu Province, 214000, Department of Pathology, The First Affiliated Hospital of University of South China, Hengyang City, Hunan Province, 421001



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