title: Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes.
abstract: Arterial smooth muscle cells (ASMCs) undergo phenotypic changes during development and pathological processes in vivo and during cell culture in vitro. Our previous studies demonstrated that retrovirally mediated expression of the versican V3 splice variant (V3) by ASMCs retards cell proliferation and migration in vitro and reduces neointimal thickening and macrophage and lipid accumulation in animal models of vascular injury and atherosclerosis. However, the molecular pathways induced by V3 expression that are responsible for these changes are not yet clear. In this study, we employed a microarray approach to examine how expression of V3 induced changes in gene expression and the molecular pathways in rat ASMCs. We found that forced expression of V3 by ASMCs affected expression of 521 genes by more than 1.5-fold. Gene ontology analysis showed that components of the extracellular matrix were the most significantly affected by V3 expression. In addition, genes regulating the formation of the cytoskeleton, which also serve as markers of contractile smooth muscle cells (SMCs), were significantly up-regulated. In contrast, components of the complement system, chemokines, chemokine receptors, and transcription factors crucial for regulating inflammatory processes were among the genes most down-regulated. Consistently, we found that the level of myocardin, a key transcription factor promoting contractile SMC phenotype, was greatly increased, and the proinflammatory transcription factors NFκB1 and CCAAT/enhancer-binding protein β were significantly attenuated in V3-expressing SMCs. Overall, these findings demonstrate that V3 expression reprograms ASMCs promoting differentiated and anti-inflammatory phenotypes.
authors.affiliation: From the Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101 and.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Kang
authors.affiliation: the Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Barth
authors.affiliation: the Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Erin P
authors.initials: EP
authors.lastname: Sproul
authors.affiliation: From the Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101 and.
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Yoon
authors.affiliation: From the Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101 and.
authors.forename: Gail A
authors.initials: GA
authors.lastname: Workman
authors.affiliation: From the Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101 and.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Braun
authors.affiliation: the Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: W Scott
authors.initials: WS
authors.lastname: Argraves
authors.affiliation: From the Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101 and twight@benaroyaresearch.org.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001158:Arteries / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D060833:Cellular Microenvironment; D016000:Cluster Analysis; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D058977:Molecular Sequence Annotation; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011916:Rats, Inbred F344; D020218:Response Elements / Q000235:genetics; D012984:Software; D015854:Up-Regulation / Q000235:genetics; D053675:Versicans / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D053675:Versicans
keywords: differentiation; extracellular matrix; inflammation; inflammatory bowel disease (IBD); microarray; proteoglycan; proteoglycan structure; versican (VCAN)