title: Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin polymerization and vascular injury.
abstract: OBJECTIVE
  Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype.
  
  
  RESULTS
  Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function.
  
  
  CONCLUSIONS
  This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells.
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Karolina M
authors: KM
authors: Turczyńska
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Karl
authors: K
authors: Swärd
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Tran Thi
authors: TT
authors: Hien
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Johan
authors: J
authors: Wohlfahrt
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Ingrid Yao
authors: IY
authors: Mattisson
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Mari
authors: M
authors: Ekman
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Johan
authors: J
authors: Nilsson
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Johan
authors: J
authors: Sjögren
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Vignesh
authors: V
authors: Murugesan
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Anna
authors: A
authors: Hultgårdh-Nilsson
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Pilar
authors: P
authors: Cidad
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: Per
authors: P
authors: Hellstrand
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.).
authors: M Teresa
authors: MT
authors: Pérez-García
authors: From the Department of Experimental Medical Science (K.M.T., K.S., T.T.H., J.W., I.Y.M., M.E., V.M., A.H.-N., P.H., S.A.) and Department of Clinical Science (J.N., J.S.), Lund University, Lund, Sweden; and Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain (P.C., M.T.P.-G.). sebastian.albinsson@med.lu.se.
authors: Sebastian
authors: S
authors: Albinsson
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000293:injuries; D002478:Cells, Cultured; D016189:Dystrophin / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics*; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D058105:Polymerization; D014158:Transcription, Genetic; D014652:Vascular Diseases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000199:Actins; D016189:Dystrophin; D008840:Microfilament Proteins; C503980:Synpo2 protein, mouse
keywords: angioplasty; gene expression; vascular diseases