title: Transcriptome profiling reveals that the SM22α-regulated molecular pathways contribute to vascular pathology.
abstract: Smooth muscle cell marker, SM22α, was down-regulated in the pathogenesis of arterial diseases including atherosclerosis, restenosis and abdominal aortic aneurysms. However, the question still exists whether this down-regulation actively contributes to the pathogenesis of vascular diseases. In an ongoing effort to understand the role of SM22α, here we explored transcriptome profiling by RNA-Seq from arteries of SM22α(-/-) and SM22α(+/+) mice. Analysis revealed that the most enriched pathways caused by SM22α-knockout were hematopoiesis, inflammation and lipid metabolism, respectively, and NF-κB, RXRα and PPARα were the major upstream regulators. The candidate genes involved in inflammation and lipid metabolism were clustered in atherosclerosis. Thus we suspected that the molecular basis in SM22α(-/-) mice was already prepared for the initiation of atherosclerosis. Further analysis suggested the up-regulated TNF caused NF-κB pathway activation. Our results showed loss of SM22α exacerbated TNF-α-mediated NF-κB activation and increased the expression levels of ApoCI in vitro, while overexpression of SM22α suppressed TNF-α-mediated NF-κB activation. In addition, disruption of SM22α enhanced injury-induced neointimal hyperplasia, and increased expression levels of molecules related with cellular adhesion and extracellular matrix degradation. Taken together, these findings not only suggested down-regulation of SM22α can actively contribute to the pathogenesis of atherosclerosis from the molecular basis, but also further confirmed that the vascular cells of SM22α(-/-) mice may become more sensitive to extracellular stimulation, increasing its tendency to develop vascular diseases. Meanwhile, rescuing SM22α expression may provide a novel therapeutic strategy for arterial diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China; Department of Biochemistry and Molecular Biology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, PR China. Electronic address: hanmei@hebmu.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D053302:Apolipoprotein C-I / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics*; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058426:Neointima / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053302:Apolipoprotein C-I; D008840:Microfilament Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; C058992:Tagln protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Atherosclerosis; NF-κB; SM22α; Transcriptome profiling; Vascular inflammation