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Cell Physiol Biochem. 2017;42(6):2207-2219. doi: 10.1159/000479995. Epub 2017 Aug 16.

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7.

Author information

1
Department of Cardiology, Bayi Hospital Affiliated Nanjing University Of Chinese Medicine, Nanjing, China.
2
Department of Orthopedics, the Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract

BACKGROUND/AIMS:

Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear.

METHODS:

To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice. First, we explored the expression of miR-21 in the infarcted zone in mice model of MI via RT-qPCR. Next, we examined the effects of TGF-β1 on miR-21 expression in cardiac fibroblasts (CFs). Then, CFs were infected with miR-21 mimics or miR-21 inhibitors to investigate the effects of miR-21 on the process of CFs activation in vitro. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-21. At last, in-vivo study was done to confirm MiR-21 regulated myocardial fibrosis after MI in mice.

RESULTS:

MiR-21 was up-regulated in the infarcted zone after MI in vivo. TGF-β1 treatment increased miR-21 expression in CFs. Overexpression of miR-21 promoted the effects of TGF-β1-induced activation of CFs, evidenced by increased expression of Col-1, α-SMA and F-actin, whereas inhibition of miR-21 attenuated the process of fibrosis. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that Smad7 is a direct target of miR-21. In addition, in-vivo study revealed that MiR-21 regulated myocardial fibrosis after MI in mice.

CONCLUSION:

These findings suggested that miR-21 has a critical role in CF activation and cardiac fibrosis after MI through via TGF-β/Smad7 signaling pathway. Thus, miR-21 promises to be a potential therapy in treatment of cardiac fibrosis after MI.

KEYWORDS:

Cardiac fibrosis; Mir-21; Myocardial infarction; Smad7; TGF-β1

PMID:
28817807
DOI:
10.1159/000479995
[Indexed for MEDLINE]
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