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MicroRNA-328, a Potential Anti-Fibrotic Target in Cardiac Interstitial Fibrosis
- Source :
- Cellular Physiology and Biochemistry, Vol 39, Iss 3, Pp 827-836 (2016)
- Publication Year :
- 2016
- Publisher :
- Cell Physiol Biochem Press GmbH & Co KG, 2016.
-
Abstract
- Background/Aims: Deregulated myocardial fibrosis is associated with a wide spectrum of cardiac conditions, being considered one of the major causes for heart disease. Our study was designed to investigate the role of microRNA-328 (miR-328) in regulating cardiac fibrosis. Methods: We induced cardiac fibrosis following MI by occlusion of the left coronary artery in C57BL/6 mice. Real-time PCR was employed to evaluate the level of miR-328. Masson's Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA's binding site in the TGFβRIII gene. Western blot analysis was used to examine TGFβRIII, p-smad2/3 and TGF-β1 at protein level. Results: In this study, we found that miR-328 was significantly upregulated in the border zone of infarcted myocardium of wild type (WT) mice; TGFβRIII was downregulated whereas TGF-β1 was upregulated along with increased cardiac fibrosis. And miR-328 stimulated TGF-β1 signaling and promoted collagen production in cultured fibroblasts. We further found that the pro-fibrotic effect of miR-328 was mediated by targeting TGFβRIII. Additionally, cardiac fibrosis was significantly reduced in infarcted heart when treated with miR-328 antisense. Conclusions: These data suggest that miR-328 is a potent pro-fibrotic miRNA and an important determinant of cardiac fibrosis in diseased heart.
- Subjects :
- 0301 basic medicine
Male
Pathology
Heart disease
Physiology
Cardiac fibrosis
Myocardial Infarction
Smad2 Protein
MiR-328
lcsh:Physiology
Mice
Fibrosis
Genes, Reporter
lcsh:QD415-436
Myocardial infarction
Luciferases
medicine.diagnostic_test
lcsh:QP1-981
Coronary Vessels
Remodeling
Proteoglycans
Collagen
Signal Transduction
medicine.medical_specialty
Primary Cell Culture
Transforming Growth Factor beta1
lcsh:Biochemistry
03 medical and health sciences
Western blot
medicine
Animals
Trichrome stain
Smad3 Protein
business.industry
Myocardium
Fibroblasts
Oligonucleotides, Antisense
medicine.disease
Mice, Inbred C57BL
MicroRNAs
030104 developmental biology
Coronary Occlusion
Gene Expression Regulation
Coronary occlusion
Myocardial fibrosis
Gene expression
business
Receptors, Transforming Growth Factor beta
Subjects
Details
- Language :
- English
- ISSN :
- 14219778 and 10158987
- Volume :
- 39
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cellular Physiology and Biochemistry
- Accession number :
- edsair.doi.dedup.....8c2faee848b2b38f4173c41027727c7f