Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling

作者：Xiong, Xiaojv; Liu, Yu; Mei, Yang; Peng, Jianye; Wang, Zhiqiang; Kong, Bin; Zhong, Peng; Xiong, Liang; Quan, Dajun; Li, Qi; Wang, Guangji; Huang, He^*

来源：Scientific Reports, 2017, 7(1): 41857.

DOI：10.1038/srep41857

• NF-KAPPA-B
• ISCHEMIA-REPERFUSION INJURY
• HYPERTROPHIC RESPONSE
• SIGNALING PATHWAYS
• ACTIVATION
• EXPRESSION
• MD-1
• HEART
• RP105
• TOLL-LIKE-RECEPTOR-4

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-kappa B 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-kappa B 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-kappa B signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy.

• 出版日期2017-2-6
• 单位武汉大学