title: Olfactomedin 2 Regulates Smooth Muscle Phenotypic Modulation and Vascular Remodeling Through Mediating Runt-Related Transcription Factor 2 Binding to Serum Response Factor.
abstract: OBJECTIVE
  The objective of this study is to investigate the role and underlying mechanism of Olfactomedin 2 (Olfm2) in smooth muscle cell (SMC) phenotypic modulation and vascular remodeling.
  
  
  RESULTS
  Platelet-derived growth factor-BB induces Olfm2 expression in primary SMCs while modulating SMC phenotype as shown by the downregulation of SMC marker proteins. Knockdown of Olfm2 blocks platelet-derived growth factor-BB-induced SMC phenotypic modulation, proliferation, and migration. Conversely, Olfm2 overexpression inhibits SMC marker expression. Mechanistically, Olfm2 promotes the interaction of serum response factor with the runt-related transcription factor 2 that is induced by platelet-derived growth factor-BB, leading to a decreased interaction between serum response factor and myocardin, causing a repression of SMC marker gene transcription and consequently SMC phenotypic modulation. Animal studies show that Olfm2 is upregulated in balloon-injured rat carotid arteries. Knockdown of Olfm2 effectively inhibits balloon injury-induced neointima formation. Importantly, knockout of Olfm2 in mice profoundly suppresses wire injury-induced neointimal hyperplasia while restoring SMC contractile protein expression, suggesting that Olfm2 plays a critical role in SMC phenotypic modulation in vivo.
  
  
  CONCLUSIONS
  Olfm2 is a novel factor mediating SMC phenotypic modulation. Thus, Olfm2 may be a potential target for treating injury-induced proliferative vascular diseases.
authors.affiliation: From the Department of Physiology and Pharmacology, University of Georgia, Athens (N.S., C.-X.L., X.-B.C., S.-Y.C.); and Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD (S.I.T.).
authors.forename: Ning
authors.initials: N
authors.lastname: Shi
authors.affiliation: From the Department of Physiology and Pharmacology, University of Georgia, Athens (N.S., C.-X.L., X.-B.C., S.-Y.C.); and Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD (S.I.T.).
authors.forename: Chen-Xiao
authors.initials: CX
authors.lastname: Li
authors.affiliation: From the Department of Physiology and Pharmacology, University of Georgia, Athens (N.S., C.-X.L., X.-B.C., S.-Y.C.); and Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD (S.I.T.).
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Cui
authors.affiliation: From the Department of Physiology and Pharmacology, University of Georgia, Athens (N.S., C.-X.L., X.-B.C., S.-Y.C.); and Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD (S.I.T.).
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Tomarev
authors.affiliation: From the Department of Physiology and Pharmacology, University of Georgia, Athens (N.S., C.-X.L., X.-B.C., S.-Y.C.); and Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD (S.I.T.). sc229@uga.edu.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D058426:Neointima; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D066253:Vascular Remodeling / Q000187:drug effects; D000099251:Myocardin
chemical_list: D000077214:Becaplermin; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; D009687:Nuclear Proteins; D020574:Proto-Oncogene Proteins c-sis; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin; C493717:Runx2 protein, rat; C000620713:olfactomedin 2, rat; C000620714:serum response factor, rat
keywords: carotid arteries; contractile proteins; hyperplasia; neointima; vascular remodeling