| First Author | Wang C | Year | 2017 |
| Journal | Mol Ther | Volume | 25 |
| Issue | 1 | Pages | 192-204 |
| PubMed ID | 28129114 | Mgi Jnum | J:331333 |
| Mgi Id | MGI:6851163 | Doi | 10.1016/j.ymthe.2016.09.001 |
| Citation | Wang C, et al. (2017) Macrophage-Derived mir-155-Containing Exosomes Suppress Fibroblast Proliferation and Promote Fibroblast Inflammation during Cardiac Injury. Mol Ther 25(1):192-204 |
| abstractText | Inflammation plays an important role in cardiac injuries. Here, we examined the role of miRNA in regulating inflammation and cardiac injury during myocardial infarction. We showed that mir-155 expression was increased in the mouse heart after myocardial infarction. Upregulated mir-155 was primarily presented in macrophages and cardiac fibroblasts of injured hearts, while pri-mir-155 was only expressed in macrophages. mir-155 was also presented in exosomes derived from macrophages, and it can be transferred into cardiac fibroblasts by macrophage-derived exosomes. A mir-155 mimic or mir-155 containing exosomes inhibited cardiac fibroblast proliferation by downregulating Son of Sevenless 1 expression and promoted inflammation by decreasing Suppressor of Cytokine Signaling 1 expression. These effects were reversed by the addition of a mir-155 inhibitor. In vivo, mir-155-deficient mice showed a significant reduction of the incidence of cardiac rupture and an improved cardiac function compared with wild-type mice. Moreover, transfusion of wild-type macrophage exosomes to mir-155(-/-) mice exacerbated cardiac rupture. Finally, the mir-155-deficient mice exhibited elevated fibroblast proliferation and collagen production, along with reduced cardiac inflammation in injured heart. Taken together, our results demonstrate that activated macrophages secrete mir-155-enriched exosomes and identify macrophage-derived mir-155 as a paracrine regulator for fibroblast proliferation and inflammation; thus, a mir-155 inhibitor (i.e., mir-155 antagomir) has the potential to be a therapeutic agent for reducing acute myocardial-infarction-related adverse events. |
