| First Author | Teng L | Year | 2021 |
| Journal | J Cell Mol Med | Volume | 25 |
| Issue | 1 | Pages | 73-83 |
| PubMed ID | 33215816 | Mgi Jnum | J:345171 |
| Mgi Id | MGI:6803403 | Doi | 10.1111/jcmm.15814 |
| Citation | Teng L, et al. (2021) Cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating Early Growth Response Protein 3 (EGR3). J Cell Mol Med 25(1):73-83 |
| abstractText | Pathological myocardial fibrosis and hypertrophy occur due to chronic cardiac stress. The microRNA-27a (miR-27a) regulates collagen production across diverse cell types and organs to inhibit fibrosis and could constitute an important therapeutic avenue. However, its impact on hypertrophy and cardiac remodelling is less well-known. We employed a transverse aortic constriction (TAC) murine model of left ventricular pressure overload to investigate the in vivo effects of genetic miR-27a knockout, antisense inhibition of miR-27a-5p and fibroblast-specific miR-27a knockdown or overexpression. In silico Venn analysis and reporter assays were used to identify miR-27a-5p's targeting of Early Growth Response Protein 3 (Egr3). We evaluated the effects of miR-27a-5p and Egr3 upon transforming growth factor-beta (Tgf-beta) signalling and secretome of cardiac fibroblasts in vitro. miR-27a-5p attenuated TAC-induced cardiac fibrosis and myofibroblast activation in vivo, without a discernible effect on cardiac myocytes. Molecularly, miR-27a-5p inhibited transforming growth factor-beta (Tgf-beta) signalling and pro-fibrotic protein secretion in cardiac fibroblasts in vitro through suppressing the pro-fibrotic transcription factor Early Growth Response Protein 3 (Egr3). This body of work suggests that cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating Egr3 expression. |
