| First Author | Xiong X | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 41857 | PubMed ID | 28165494 |
| Mgi Jnum | J:275285 | Mgi Id | MGI:6296418 |
| Doi | 10.1038/srep41857 | Citation | Xiong X, et al. (2017) Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling. Sci Rep 7:41857 |
| abstractText | Myeloid differentiation 1 (MD-1), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. Previous studies showed that MD-1 may be restricted in the immune system. In this study, we demonstrated for the first time that MD-1 was highly expressed in both human and animal hearts. We also discovered that cardiac-specific overexpression of MD-1 significantly attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of MD-1 had the opposite effects. Similar results were observed for in vitro angiotensin II-induced neonatal rat cardiomyocyte hypertrophy. The antihypertrophic effects of MD-1 under hypertrophic stimuli were associated with the blockage of MEK-ERK 1/2 and NF-kappaB signalling. Blocking MEK-ERK 1/2 signalling with a pharmacological inhibitor (U0126) greatly attenuated the detrimental effects observed in MD-1 knockout cardiomyocytes exposed to angiotensin II stimuli. Similar results were observed by blocking NF-kappaB signalling with a pharmacological inhibitor (BAY11-7082). Our data indicate that MD-1 inhibits cardiac hypertrophy and suppresses cardiac dysfunction during the remodelling process, which is dependent on its modulation of the MEK-ERK 1/2 and NF-kappaB signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy. |
