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MicroRNA-328, a Potential Anti-Fibrotic Target in Cardiac Interstitial Fibrosis.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2016; Vol. 39 (3), pp. 827-36. Date of Electronic Publication: 2016 Aug 09. - Publication Year :
- 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.<br />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.<br />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.<br />Conclusions: These data suggest that miR-328 is a potent pro-fibrotic miRNA and an important determinant of cardiac fibrosis in diseased heart.<br /> (© 2016 The Author(s) Published by S. Karger AG, Basel.)
- Subjects :
- Animals
Collagen genetics
Collagen metabolism
Coronary Occlusion pathology
Coronary Occlusion surgery
Coronary Vessels pathology
Coronary Vessels surgery
Fibroblasts pathology
Fibrosis
Gene Expression Regulation
Genes, Reporter
Luciferases genetics
Luciferases metabolism
Male
Mice
Mice, Inbred C57BL
MicroRNAs antagonists & inhibitors
MicroRNAs metabolism
Myocardial Infarction metabolism
Myocardial Infarction pathology
Myocardium pathology
Oligonucleotides, Antisense genetics
Oligonucleotides, Antisense metabolism
Primary Cell Culture
Proteoglycans metabolism
Receptors, Transforming Growth Factor beta metabolism
Signal Transduction
Smad2 Protein genetics
Smad2 Protein metabolism
Smad3 Protein genetics
Smad3 Protein metabolism
Transforming Growth Factor beta1 metabolism
Fibroblasts metabolism
MicroRNAs genetics
Myocardial Infarction genetics
Myocardium metabolism
Proteoglycans genetics
Receptors, Transforming Growth Factor beta genetics
Transforming Growth Factor beta1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 39
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27497782
- Full Text :
- https://doi.org/10.1159/000447793