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Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7
- Source :
- Cellular Physiology and Biochemistry, Vol 42, Iss 6, Pp 2207-2219 (2017)
- Publication Year :
- 2017
- Publisher :
- Cell Physiol Biochem Press GmbH & Co KG, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Physiology
Cardiac fibrosis
Cell Survival
Mir-21
lcsh:Physiology
Smad7 Protein
Rats, Sprague-Dawley
Transforming Growth Factor beta1
lcsh:Biochemistry
03 medical and health sciences
Mice
Western blot
In vivo
Fibrosis
Internal medicine
TGF-β1
medicine
Animals
lcsh:QD415-436
Myocardial infarction
Cells, Cultured
medicine.diagnostic_test
Smad7
lcsh:QP1-981
business.industry
Myocardium
Antagomirs
Fibroblasts
medicine.disease
Pathophysiology
Rats
Up-Regulation
Mice, Inbred C57BL
Disease Models, Animal
MicroRNAs
030104 developmental biology
Cancer research
Cardiology
Myocardial fibrosis
RNA Interference
Signal transduction
business
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 14219778 and 10158987
- Volume :
- 42
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cellular Physiology and Biochemistry
- Accession number :
- edsair.doi.dedup.....f59b9cfe72ffa52669594bd84cdc431c