| First Author | Liang H | Year | 2012 |
| Journal | Int J Biochem Cell Biol | Volume | 44 |
| Issue | 12 | Pages | 2152-60 |
| PubMed ID | 22960625 | Mgi Jnum | J:224728 |
| Mgi Id | MGI:5688831 | Doi | 10.1016/j.biocel.2012.08.019 |
| Citation | Liang H, et al. (2012) A novel reciprocal loop between microRNA-21 and TGFbetaRIII is involved in cardiac fibrosis. Int J Biochem Cell Biol 44(12):2152-60 |
| abstractText | Cardiac fibrosis is characterized by aberrant proliferation of cardiac fibroblasts and exaggerated deposition of extracellular matrix (ECM) in the myocardial interstitial, and ultimately impairs cardiac function. It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis. Our previous study confirmed that transforming growth factor beta receptor III (TGFbetaRIII) is a negative regulator of TGF-beta pathway. Here, we aimed to decipher the relationship between miR-21 and TGFbetaRIII in the pathogenic process of myocardial fibrosis. We found that TGF-beta1 and miR-21 were up-regulated, whereas TGFbetaRIII was down-regulated in the border zone of mouse hearts in response to myocardial infarction. After transfection of miR-21 into cardiac fibroblasts, TGFbetaRIII expression was markedly reduced and collagen content was increased. And, luciferase results confirmed that TGFbetaRIII was a target of miR-21. It suggests that up-regulation of miR-21 could increase the collagen content and at least in part through inhibiting TGFbetaRIII. Conversely, we also confirmed that overexpression of TGFbetaRIII could inhibit the expression of miR-21 and reduce collagen production in fibroblasts. Further studies showed that overexpression of TGFbetaRIII could also deactivate TGF-beta1 pathway by decreasing the expression of TGF-beta1 and phosphorylated-Smad3 (p-Smad3). TGF-beta1 has been proven as a positive regulator of miR-21. Taken together, we found a novel reciprocal loop between miR-21 and TGFbetaRIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling. |
