| First Author | Hu J | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 13 | Pages | 6172-6180 |
| PubMed ID | 30867288 | Mgi Jnum | J:273868 |
| Mgi Id | MGI:6286167 | Doi | 10.1073/pnas.1822176116 |
| Citation | Hu J, et al. (2019) RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure. Proc Natl Acad Sci U S A 116(13):6172-6180 |
| abstractText | Heart performance relies on highly coordinated excitation-contraction (EC) coupling, and defects in this critical process may be exacerbated by additional genetic defects and/or environmental insults to cause eventual heart failure. Here we report a regulatory pathway consisting of the RNA binding protein RBFox2, a stress-induced microRNA miR-34a, and the essential EC coupler JPH2. In this pathway, initial cardiac defects diminish RBFox2 expression, which induces transcriptional repression of miR-34a, and elevated miR-34a targets Jph2 to impair EC coupling, which further manifests heart dysfunction, leading to progressive heart failure. The key contribution of miR-34a to this process is further established by administrating its mimic, which is sufficient to induce cardiac defects, and by using its antagomir to alleviate RBFox2 depletion-induced heart dysfunction. These findings elucidate a potential feed-forward mechanism to account for a critical transition to cardiac decompensation and suggest a potential therapeutic avenue against heart failure. |
