| First Author | Valussi M | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 42 | Pages | eabi6648 |
| PubMed ID | 34644107 | Mgi Jnum | J:312355 |
| Mgi Id | MGI:6784103 | Doi | 10.1126/sciadv.abi6648 |
| Citation | Valussi M, et al. (2021) Repression of Osmr and Fgfr1 by miR-1/133a prevents cardiomyocyte dedifferentiation and cell cycle entry in the adult heart. Sci Adv 7(42):eabi6648 |
| abstractText | Dedifferentiation of cardiomyocytes is part of the survival program in the remodeling myocardium and may be essential for enabling cardiomyocyte proliferation. In addition to transcriptional processes, non-coding RNAs play important functions for the control of cell cycle regulation in cardiomyocytes and cardiac regeneration. Here, we demonstrate that suppression of FGFR1 and OSMR by miR-1/133a is instrumental to prevent cardiomyocyte dedifferentiation and cell cycle entry in the adult heart. Concomitant inactivation of both miR-1/133a clusters in adult cardiomyocytes activates expression of cell cycle regulators, induces a switch from fatty acid to glycolytic metabolism, and changes expression of extracellular matrix genes. Inhibition of FGFR and OSMR pathways prevents most effects of miR-1/133a inactivation. Short-term miR-1/133a depletion protects cardiomyocytes against ischemia, while extended loss of miR-1/133a causes heart failure. Our results demonstrate a crucial role of miR-1/133aâmediated suppression of Osmr and Ffgfr1 in maintaining the postmitotic differentiated state of cardiomyocytes. |
