SM22α inhibits vascular inflammation via stabilization of IκBα in vascular smooth muscle cells.
J Mol Cell Cardiol
; 84: 191-9, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25937534
ABSTRACT
Smooth muscle (SM) 22α, an actin-binding protein, is down-regulated in atherosclerotic arteries. Disruption of SM22α promotes arterial inflammation through activation of reactive oxygen species (ROS)-mediated nuclear factor (NF)-κB pathways. This study aimed to investigate the mechanisms by which SM22α regulates vascular inflammatory response. The ligation injury model of SM22α(-/-) mice displayed up-regulation of inflammatory molecules MCP-1, VCAM-1, and ICAM-1 in the carotid arteries. Similar results were discovered in human atherosclerotic samples. In vitro studies, overexpression of SM22α attenuated TNF-α-induced IκBα phosphorylation and degradation, accompanied by decreased NF-κB activity and reduced inflammatory molecule expression. Using coimmunoprecipitation, we found that SM22α interacted with and stabilized IκBα in quiescent VSMCs. Upon TNF-α stimulation, SM22α was phosphorylated by casein kinase (CK) II at Thr139, leading to dissociation of SM22α from IκBα, followed by IκBα degradation and NF-κB activation. Our findings demonstrate that SM22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signaling cascades. SM22α may be a novel therapeutic target for human vascular diseases and other inflammatory conditions.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas I-kappa B
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Miócitos de Músculo Liso
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Inflamação
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Proteínas dos Microfilamentos
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Proteínas Musculares
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article