title: HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box.
abstract: OBJECTIVE
  Myocardin is a coactivator of serum response factor (SRF) required for vascular smooth muscle cell (VSMC) differentiation. HERP1 is a transcriptional repressor, which is abundantly expressed in vascular system and is known to function as a target gene of Notch. However, the role of HERP1 in the pathogenesis of vascular lesions remains unknown. The present study characterizes the expression of HERP1 in normal and diseased vessels, and tests the hypothesis that HERP1 inhibits SRF/myocardin-dependent SMC gene expression.
  
  
  RESULTS
  Immunohistochemistry revealed that HERP1 and myocardin expression was localized to SMC in the neointima of balloon-injured rat aorta and in human coronary atherosclerotic lesions. Expression of both HERP1 and myocardin was elevated in cultured VSMCs compared with medial SMC. Overexpressed HERP1 inhibited the myocardin-induced SMC marker gene expression in 10T1/2 cells. HERP1 protein interfered with the SRF/CArG-box interaction in vivo and in vitro. Immunoprecipitation assays showed that HERP1 physically interacts with SRF.
  
  
  CONCLUSIONS
  HERP1 expression was associated with the SMC proliferation and dedifferentiation in vitro and in vivo. HERP1 may play a role in promoting the phenotypic modulation of VSMCs during vascular injury and atherosclerotic process by interfering with SRF binding to CArG-box through physical association between HERP1 and SRF.
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iso
authors.forename: Miki
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Akiyama
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kanai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sato
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawai-Kowase
authors.forename: Toru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Maeno
authors.forename: Ei-ichi
authors.initials: E
authors.lastname: Okamoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Arai
authors.forename: Larry
authors.initials: L
authors.lastname: Kedes
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000328:Adult; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000293:injuries / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017225:Atherectomy, Coronary; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003331:Coronary Vessels / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism*; D024745:Smooth Muscle Myosins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D000099251:Myocardin
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005819:Genetic Markers; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018995:Myosin Heavy Chains; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D026362:Serum Response Factor; D024745:Smooth Muscle Myosins; D015534:Trans-Activators; D000099251:Myocardin; C405693:HEY2 protein, human; C476858:SRF protein, human; C051615:transgelin