title: Syndecan-1 regulates vascular smooth muscle cell phenotype.
abstract: OBJECTIVE
  We examined the role of syndecan-1 in modulating the phenotype of vascular smooth muscle cells in the context of endogenous inflammatory factors and altered microenvironments that occur in disease or injury-induced vascular remodeling.
  
  
  RESULTS
  Vascular smooth muscle cells (vSMCs) display a continuum of phenotypes that can be altered during vascular remodeling. While the syndecans have emerged as powerful and complex regulators of cell function, their role in controlling vSMC phenotype is unknown. Here, we isolated vSMCs from wild type (WT) and syndecan-1 knockout (S1KO) mice. Gene expression and western blotting studies indicated decreased levels of α-smooth muscle actin (α-SMA), calponin, and other vSMC-specific differentiation markers in S1KO relative to WT cells. The spread area of the S1KO cells was found to be greater than WT cells, with a corresponding increase in focal adhesion formation, Src phosphorylation, and alterations in actin cytoskeletal arrangement. In addition, S1KO led to increased S6RP phosphorylation and decreased AKT and PKC-α phosphorylation. To examine whether these changes were present in vivo, isolated aortae from aged WT and S1KO mice were stained for calponin. Consistent with our in-vitro findings, the WT mice aortae stained higher for calponin relative to S1KO. When exposed to the inflammatory cytokine TNF-α, WT vSMCs had an 80% reduction in syndecan-1 expression. Further, with TNF-α, S1KO vSMCs produced increased pro-inflammatory cytokines relative to WT. Finally, inhibition of interactions between syndecan-1 and integrins αvβ3 and αvβ5 using the inhibitory peptide synstatin appeared to have similar effects on vSMCs as knocking out syndecan-1, with decreased expression of vSMC differentiation markers and increased expression of inflammatory cytokines, receptors, and osteopontin.
  
  
  CONCLUSIONS
  Taken together, our results support that syndecan-1 promotes vSMC differentiation and quiescence. Thus, the presence of syndecan-1 would have a protective effect against vSMC dedifferentiation and this activity is linked to interactions with integrins αvβ3 and αvβ5.
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Somali
authors.initials: S
authors.lastname: Chaterji
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Christoffer H
authors.initials: CH
authors.lastname: Lam
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Ho
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Proske
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Baker
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010641:Phenotype; D010766:Phosphorylation; D019030:Receptors, Vitronectin / Q000378:metabolism; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D039302:Integrin alphaVbeta3; D008840:Microfilament Proteins; D019030:Receptors, Vitronectin; D053668:Syndecan-1; D000096985:Calponins; C558396:Acta2 protein, mouse; C508242:Sdc1 protein, mouse; C064660:integrin alphaVbeta5