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Published on: June 15, 2018
MicroRNA-130a, a Potential Antifibrotic Target in Cardiac Fibrosis
Li Li1,2, Kelsey R Bounds3, Piyali Chatterjee3
1Department of Medical Physiology, Texas A & M Health Science Center, Central Texas Veterans Health Care System, Temple, TX.
Background:
Cardiac fibrosis occurs because of disruption of the extracellular matrix network leading to myocardial dysfunction. Angiotensin II has been implicated in the development of cardiac fibrosis. Recently, microRNAs have been identified as an attractive target for therapeutic intervention in cardiac pathologies; however, the underlying mechanism of microRNAs in cardiac fibrosis remains unclear. MicroRNA-130a (miR-130a) has been shown to participate in angiogenesis and cardiac arrhythmia; however, its role in cardiac fibrosis is unknown.
Methods And Results:
In this study, we found that miR-130a was significantly upregulated in angiotensin II-infused mice. The in vivo inhibition of miR-130a by locked nucleic acid- based anti-miR-130a in mice significantly reduced angiotensin II-induced cardiac fibrosis. Upregulation of miR-130a was confirmed in failing human hearts. Overexpressing miR-130a in cardiac fibroblasts promoted profibrotic gene expression and myofibroblasts differentiation, and the inhibition of miR-130a reversed the processes. Using the constitutive and dominant negative constructs of peroxisome proliferator-activated receptor γ 3-'untranslated region (UTR), data revealed that the protective mechanism was associated with restoration of peroxisome proliferator-activated receptor γ level leading to the inhibition of angiotensin II-induced cardiac fibrosis.
Conclusions:
Our findings provide evidence that miR-130a plays a critical role in cardiac fibrosis by directly targeting peroxisome proliferator-activated receptor γ. We conclude that inhibition of miR-130a would be a promising strategy for the treatment of cardiac fibrosis.
Insights
MicroRNA-130a (miR-130a) promotes cardiac fibrosis by targeting peroxisome proliferator-activated receptor γ. Inhibiting miR-130a reduces fibrosis, offering a potential therapeutic strategy for heart conditions.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Fibrosis Research
Background:
- Cardiac fibrosis disrupts the extracellular matrix, leading to myocardial dysfunction.
- Angiotensin II is implicated in cardiac fibrosis development.
- The role of microRNAs in cardiac fibrosis is largely unknown, despite their therapeutic potential.
Purpose of the Study:
- To investigate the role of microRNA-130a (miR-130a) in angiotensin II-induced cardiac fibrosis.
- To elucidate the underlying molecular mechanism of miR-130a in cardiac fibrosis.
Main Methods:
- Upregulation of miR-130a was assessed in angiotensin II-infused mice and failing human hearts.
- In vivo inhibition of miR-130a was performed using locked nucleic acid-based anti-miR-130a.
- The effect of miR-130a manipulation on cardiac fibroblasts and peroxisome proliferator-activated receptor γ (PPARγ) was examined.
Main Results:
- miR-130a was significantly upregulated in angiotensin II-treated mice and human failing hearts.
- Inhibition of miR-130a in mice reduced angiotensin II-induced cardiac fibrosis.
- Overexpression of miR-130a promoted profibrotic gene expression and myofibroblast differentiation in cardiac fibroblasts, while inhibition reversed these effects.
- The protective mechanism involved the restoration of peroxisome proliferator-activated receptor γ (PPARγ) levels.
Conclusions:
- miR-130a plays a critical role in cardiac fibrosis by directly targeting PPARγ.
- Inhibition of miR-130a represents a promising therapeutic strategy for treating cardiac fibrosis.
