| First Author | Zheng G | Year | 2019 |
| Journal | Protein Cell | Volume | 10 |
| Issue | 2 | Pages | 104-119 |
| PubMed ID | 29980933 | Mgi Jnum | J:289209 |
| Mgi Id | MGI:6434670 | Doi | 10.1007/s13238-018-0563-2 |
| Citation | Zheng G, et al. (2019) TMEM43-S358L mutation enhances NF-kappaB-TGFbeta signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Protein Cell 10(2):104-119 |
| abstractText | Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor kappaB (NF-kappaB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-kappaB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFbeta1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-kappaB-TGFbeta signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development. |
