Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling.
Sci Rep
; 7: 41857, 2017 02 06.
Article
em En
| MEDLINE
| ID: mdl-28165494
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Cardiomegalia
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Remodelação Ventricular
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Antígenos de Superfície
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2017
Tipo de documento:
Article