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Published on: June 15, 2018
MicroRNA-328, a Potential Anti-Fibrotic Target in Cardiac Interstitial Fibrosis
Weijie Du1, Haihai Liang, Xu Gao
1Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, P. R. China.
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.
Insights
MicroRNA-328 (miR-328) promotes cardiac fibrosis by targeting TGFβRIII, leading to increased collagen production. Inhibiting miR-328 reduced fibrosis in mouse models, suggesting its role in heart disease.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Fibrosis Research
Background:
- Deregulated myocardial fibrosis is a key factor in various heart conditions.
- MicroRNAs play crucial roles in regulating cardiac function and disease progression.
Purpose of the Study:
- To investigate the role of microRNA-328 (miR-328) in the regulation of cardiac fibrosis.
- To elucidate the molecular mechanisms underlying miR-328's function in the heart.
Main Methods:
- Cardiac fibrosis induced by myocardial infarction (MI) in C57BL/6 mice.
- Quantification of miR-328 levels using real-time PCR.
- Assessment of fibrosis via Masson's Trichrome staining.
- Analysis of protein expression (TGFβRIII, TGF-β1) using Western blot.
Main Results:
- miR-328 was upregulated in infarcted mouse hearts, correlating with increased cardiac fibrosis.
- miR-328 targeted and downregulated TGFβRIII, while upregulating TGF-β1 signaling and collagen production.
- Inhibition of miR-328 using antisense oligonucleotides significantly reduced cardiac fibrosis.
Conclusions:
- miR-328 acts as a pro-fibrotic microRNA in the context of heart disease.
- Targeting miR-328 presents a potential therapeutic strategy for mitigating cardiac fibrosis.
