title: The profibrotic cytokine transforming growth factor-β1 increases endothelial progenitor cell angiogenic properties.
abstract: BACKGROUND
  Transforming growth factor-β1 (TGF-β1) is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), are associated with vascular remodeling, and as endothelial progenitor cells (EPCs) may be involved in this process, we investigated the impact of TGF-β1 modulation of EPC angiogenic properties.
  
  
  METHODS
  TGF-β1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-β1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on endothelial colony-forming cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-β1 in ECFCs by using short interfering RNA.
  
  
  RESULTS
  Total TGF-β1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-β1 had proangiogenic effects in vivo by increasing hemoglobin content and blood vessel formation in Matrigel plugs implanted in C57/Bl6 mice, and in vitro by enhancing ECFC viability and migration. The effects were abolished by silencing the three main TGF-β1 receptors.
  
  
  CONCLUSIONS
  TGF-β1 is proangiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-β1 may play a role during vascular remodeling in fibrotic disease states via EPCs.
authors.affiliation: Université Paris Descartes, Paris, France.
authors.forename: S M
authors.initials: SM
authors.lastname: Evrard
authors.forename: C
authors.initials: C
authors.lastname: d'Audigier
authors.forename: L
authors.initials: L
authors.lastname: Mauge
authors.forename: D
authors.initials: D
authors.lastname: Israël-Biet
authors.forename: C L
authors.initials: CL
authors.lastname: Guerin
authors.forename: I
authors.initials: I
authors.lastname: Bieche
authors.forename: J C
authors.initials: JC
authors.lastname: Kovacic
authors.forename: A-M
authors.initials: AM
authors.lastname: Fischer
authors.forename: P
authors.initials: P
authors.lastname: Gaussem
authors.forename: D M
authors.initials: DM
authors.lastname: Smadja
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005602:France; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D011446:Prospective Studies; D034622:RNA Interference; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D006454:Hemoglobins; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1