Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling

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 th...

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Published in:Scientific reports 2017-02, Vol.7 (1), p.41857-41857, Article 41857
Main Authors: Xiong, Xiaojv, Liu, Yu, Mei, Yang, Peng, Jianye, Wang, Zhiqiang, Kong, Bin, Zhong, Peng, Xiong, Liang, Quan, Dajun, Li, Qi, Wang, Guangji, Huang, He
Format: Article
Language:English
Subjects:
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82/83
Angiotensin
Angiotensin II
Cardiomyocytes
Fibrosis
Heart diseases
Humanities and Social Sciences
Hypertrophy
Immune system
multidisciplinary
Neonates
Rodents
Science
Signal transduction
TLR4 protein
Toll-like receptors
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Summary: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-κB 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-κB 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-κB signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep41857