MiR 22 may Suppress Fibrogenesis by Targeting TGFbR I in Cardiac Fibroblasts
Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR 22 might be a potential target. However, the roles and mechanisms of miR 22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR 22 in cardiac fibrosis. Methods: After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR 22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, a SMA and TGFbRI proteins levels, and real time PCR was employed to measure the Col1a1, Col3a1, miR 22 and TGFbRI mRNA levels. Results: In this study, we found that miR 22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR 22 with AMO 22 resulted in increased expression of Col1a1, Col3a1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR 22 in cultured cardiac fibroblasts significantly abrogated angiotensin II induced collagen formation and fibrogenesis. Furthermore, we found that TGFbRI is a direct target for miR 22, and downregulation of TGFbR may have mediated the antifibrotic effect of miR 22. Conclusion: Our data clearly demonstrate that miR 22 acts as a novel negative regulator of angiotensin II induced cardiac fibrosis by suppressing the expression of TGFbRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.
Cellular Physiology and Biochemistry