title: Formin mDia1 mediates vascular remodeling via integration of oxidative and signal transduction pathways.
abstract: BACKGROUND
  The mammalian diaphanous-related formin (mDia1), governs microtubule and microfilament dynamics while functioning as an effector for Rho small GTP-binding proteins during key cellular processes such as adhesion, cytokinesis, cell polarity, and morphogenesis. The cytoplasmic domain of the receptor for advanced glycation endproducts binds to the formin homology 1 domain of mDia1; mDia1 is required for receptor for advanced glycation endproducts ligand-induced cellular migration in transformed cells.
  
  
  OBJECTIVE
  Because a key mechanism in vascular remodeling is the induction of smooth muscle cell migration, we tested the role of mDia1 in this process.
  
  
  RESULTS
  We report that endothelial denudation injury to the murine femoral artery significantly upregulates mDia1 mRNA transcripts and protein in the injured vessel, particularly in vascular smooth muscle cells within the expanding neointima. Loss of mDia1 expression significantly reduces pathological neointimal expansion consequent to injury. In primary murine aortic smooth muscle cells, mDia1 is required for receptor for advanced glycation endproducts ligand-induced membrane translocation of c-Src, which leads to Rac1 activation, redox phosphorylation of AKT/glycogen synthase kinase 3β, and consequent smooth muscle cell migration.
  
  
  CONCLUSIONS
  We conclude that mDia1 integrates oxidative and signal transduction pathways triggered, at least in part, by receptor for advanced glycation endproducts ligands, thereby regulating pathological neointimal expansion.
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Fatouma
authors.initials: F
authors.lastname: Touré
authors.forename: Günter
authors.initials: G
authors.lastname: Fritz
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Vivek
authors.initials: V
authors.lastname: Rai
authors.forename: Gurdip
authors.initials: G
authors.lastname: Daffu
authors.forename: Yu Shan
authors.initials: YS
authors.lastname: Zou
authors.forename: Rosa
authors.initials: R
authors.lastname: Rosario
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Alberts
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D000080865:Formins; D017127:Glycation End Products, Advanced / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008870:Microtubules / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000074624:NADPH Oxidase 1; D058426:Neointima / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D016392:Proto-Oncogene Proteins pp60(c-src); D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3