title: The differential proliferative response of fetal and adult human skin fibroblasts to TGF-β is retained when cultured in the presence of fibronectin or collagen.
abstract: BACKGROUND
  Transforming growth factor-β is a multifunctional and pleiotropic factor with decisive role in tissue repair. In this context, we have shown previously that TGF-β inhibits the proliferation of fetal human skin fibroblasts but stimulates that of adult ones. Given the dynamic reciprocity between fibroblasts, growth factors and extracellular matrix (ECM) in tissue homeostasis, the present study aims to investigate the role of fibronectin and collagen in the proliferative effects of TGF-β on fetal and adult cells.
  
  
  METHODS
  Human fetal and adult skin fibroblasts were grown either on plastic surfaces or on surfaces coated with fibronectin or collagen type-I, as well as, on top or within three-dimensional matrices of polymerized collagen. Their proliferative response to TGF-β was studied using tritiated thymidine incorporation, while the signaling pathways involved were investigated by Western analysis and using specific kinase inhibitors.
  
  
  RESULTS
  Fetal skin fibroblast-proliferation was inhibited by TGF-β, while that of adult cells was stimulated by this factor, irrespective of the presence of fibronectin or collagen. Both inhibitory and stimulatory activities of TGF-β on the proliferation of fetal and adult fibroblasts, respectively, were abrogated when the Smad pathway was blocked. Moreover, inhibition of fetal fibroblasts was mediated by PKA activation, while stimulation of adult ones was effected through the autocrine activation of FGF receptor and the MEK-ERK pathway.
  
  
  CONCLUSIONS
  Fetal and adult human skin fibroblasts retain their differential proliferative response to TGF-β when cultured in the presence of fibronectin and unpolymerized or polymerized collagen.
  
  
  CONCLUSIONS
  The interplay between TGF-β and ECM supports the pleiotropic nature of this growth factor, in concordance with the different repair strategies between fetuses and adults. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
authors.affiliation: Laboratory for Cell Proliferation & Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Armatas
authors.affiliation: Laboratory for Cell Proliferation & Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece.
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.affiliation: Laboratory for Cell Proliferation & Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Mavrogonatou
authors.affiliation: Laboratory for Cell Proliferation & Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Angelopoulou
authors.affiliation: Laboratory for Cell Proliferation & Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Kouroumalis
authors.affiliation: Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
authors.affiliation: Laboratory for Cell Proliferation & Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece. Electronic address: dkletsas@bio.demokritos.gr.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
mesh_terms: D000328:Adult; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D005333:Fetus / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D005782:Gels; D006801:Humans; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D058105:Polymerization / Q000187:drug effects; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D005353:Fibronectins; D005782:Gels; D008934:Mitogens; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen
keywords: Adult; Collagen gel; ERK; Fetal; Fibronectin; Human skin fibroblast; PKA; Proliferation; Smad; TGF-β