MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis
BackgroundCardiac 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 c...
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| Format: | Article |
| Language: | English |
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Wiley
2017-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.006763 |
| _version_ | 1811332285327212544 |
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| author | Li Li Kelsey R. Bounds Piyali Chatterjee Sudhiranjan Gupta |
| author_facet | Li Li Kelsey R. Bounds Piyali Chatterjee Sudhiranjan Gupta |
| author_sort | Li Li |
| collection | DOAJ |
| description | BackgroundCardiac 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 ResultsIn 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. ConclusionsOur 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. |
| first_indexed | 2024-04-13T16:34:30Z |
| format | Article |
| id | doaj.art-c2422c1f198f46a4847b96cfdaad9236 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T16:34:30Z |
| publishDate | 2017-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c2422c1f198f46a4847b96cfdaad92362022-12-22T02:39:29ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-11-0161110.1161/JAHA.117.006763MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac FibrosisLi Li0Kelsey R. Bounds1Piyali Chatterjee2Sudhiranjan Gupta3Department of Medical Physiology, Texas A & M Health Science Center, Central Texas Veterans Health Care System, Temple, TXDivision of Nephrology and Hypertension, Department of Internal Medicine, Baylor Scott White Health, Temple, TXDivision of Nephrology and Hypertension, Department of Internal Medicine, Baylor Scott White Health, Temple, TXDepartment of Medical Physiology, Texas A & M Health Science Center, Central Texas Veterans Health Care System, Temple, TXBackgroundCardiac 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 ResultsIn 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. ConclusionsOur 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.https://www.ahajournals.org/doi/10.1161/JAHA.117.006763angiotensin IIcardiac fibrosismiR‐130amyofibroblastperoxisome proliferator‐activated receptor γ |
| spellingShingle | Li Li Kelsey R. Bounds Piyali Chatterjee Sudhiranjan Gupta MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiotensin II cardiac fibrosis miR‐130a myofibroblast peroxisome proliferator‐activated receptor γ |
| title | MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis |
| title_full | MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis |
| title_fullStr | MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis |
| title_full_unstemmed | MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis |
| title_short | MicroRNA‐130a, a Potential Antifibrotic Target in Cardiac Fibrosis |
| title_sort | microrna 130a a potential antifibrotic target in cardiac fibrosis |
| topic | angiotensin II cardiac fibrosis miR‐130a myofibroblast peroxisome proliferator‐activated receptor γ |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.006763 |
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