| First Author | Deng KQ | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11432 | PubMed ID | 27249321 |
| Mgi Jnum | J:239911 | Mgi Id | MGI:5882015 |
| Doi | 10.1038/ncomms11432 | Citation | Deng KQ, et al. (2016) Suppressor of IKKvarepsilon is an essential negative regulator of pathological cardiac hypertrophy. Nat Commun 7:11432 |
| abstractText | Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKvarepsilon (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. |
