title: TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration.
abstract: OBJECTIVE
  In-stent restenosis is a vascular proliferation/migration disorder characterized by hyperplasia of vascular smooth muscle cells (VSMCs). Because mounting evidence suggests that the therapeutic potential of anti-proliferation and anti-migration therapy, we investigated possible inhibitory effects of the matricellular protein TGF-beta-stimulated clone 36 (TSC-36) on vascular smooth muscle cell proliferation and migration in vitro and in vivo.
  
  
  METHODS
  Human umbilical artery smooth muscle cells (SMCs) were treated with inducting agents daidzein or estradiol. TSC-36 expression was detected by nested competitive PCR and in situ hybridization. TSC-36 was expressed in Origami (DE3) cells. The recombinant protein was used to immunize rabbits to produce polyclonal antibodies. VSMCs were treated with various concentrations of recombinant TSC-36 (rTSC-36) protein and daidzein. The MTT assay was used to analyze for cell proliferation. A transwell system was used to detect cell migration. Flow cytometry was used to detect cell phase. A rat carotid artery balloon injury model was duplicated. The rats were treated with daidzein or solvent control. Animals were sacrificed 5 weeks later, and injured arteries were taken for pathology and histology.
  
  
  RESULTS
  TSC-36 mRNA and protein expression was induced in SMCs. Cell proliferation and migration were inhibited by rTSC-36. rTSC-36 caused accumulation of SMCs in G2 phase. The inducting agent daidzein decreased neo-intima proliferation. TSC-36 mRNA and protein expression was induced and expressed in the neo-intima.
  
  
  CONCLUSIONS
  TSC-36 can be induced in VSMCs and inhibits VSMCs proliferation in vitro and in vivo.
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Luya
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.forename: Hengyi
authors.initials: H
authors.lastname: Guo
authors.forename: Renyu
authors.initials: R
authors.lastname: Sun
authors.forename: Qixia
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007529:Isoflavones / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D038702:Follistatin-Related Proteins; D007529:Isoflavones; D012333:RNA, Messenger; D011994:Recombinant Proteins; C448799:FSTL1 protein, human; C004742:daidzein