SM22α inhibits vascular inflammation via stabilization of IκBα in vascular smooth muscle cells.
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.
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Ya-Nan
YN
Shu
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Fan
F
Zhang
Cardiovascular Department of the Second Hospital, Department of Clinical Biochemistry, Hebei Medical University, Shijiazhuang 050017, PR China.
Wei
W
Bi
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Li-Hua
LH
Dong
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Dan-Dan
DD
Zhang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Rong
R
Chen
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Pin
P
Lv
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Xiao-Li
XL
Xie
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Yan-Ling
YL
Lin
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Zhen-Ying
ZY
Xue
The Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, China Administration of Education, Peking University, Beijing, PR China.
Haibo
H
Li
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Sui-Bing
SB
Miao
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Li-Li
LL
Zhao
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China.
Hong
H
Wang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Shijiazhuang 050017, PR China. Electronic address: hanmei@hebmu.edu.cn.
Mei
M
Han
D000368:Aged; D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology*; D008297:Male; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020672:I-kappa B Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D014409:Tumor Necrosis Factor-alpha; C051615:transgelin; D010769:Phosphothreonine; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D047390:Casein Kinase II
Inflammation; IκBα; SM22α; VSMC