title: Fetal and adult fibroblasts have similar TGF-beta-mediated, Smad-dependent signaling pathways.
abstract: BACKGROUND
  The scarless fetal skin-healing mechanism is mediated in part by the fibroblast and involves differential expression of transforming growth factor (TGF)-beta isoforms 1 and 3. The authors hypothesized that fetal and adult fibroblasts respond differently to TGF-beta isoform-specific stimulation, which may influence whether wounds scar. Connective tissue growth factor (CTGF), Smad3, and Smad7 are TGF-beta target genes. Expression of these targets was quantitated after TGF-beta1 and -beta3 stimulation of fetal and adult fibroblasts.
  
  
  METHODS
  Primary mouse fibroblast cultures at gestational day 16.5 (E17), 18.5 (E19), and 6 weeks (adult) were stimulated with TGF-beta1 or TGF-beta3. Quantitative polymerase chain reaction was performed for CTGF, Smad3, and Smad7 expression.
  
  
  RESULTS
  CTGF was reduced four-fold in E17 and E19 compared with adult fibroblasts (p < 0.005). After TGF-beta1 stimulation, CTGF expression increased more than 60-fold in both E17 and E19 (p < 0.01), which was three-fold greater than that in adult fibroblasts (p < 0.005). TGF-beta3 induced more than 70-fold, 50-fold, and 20-fold increases in CTGF expression in E17, E19, and adult fibroblasts, respectively (p < 0.01 for each). Both TGF-beta1 and -beta3 decreased Smad3 expression and increased Smad7 expression in each fibroblast type, suggesting that intact TGF-beta-mediated signaling pathways were present.
  
  
  CONCLUSIONS
  Fetal (E17 and E19) fibroblasts have lower CTGF expression compared with adult fibroblasts. However, fetal fibroblasts have larger increases in CTGF expression after TGF-beta1 or -beta3 stimulation. Fetal and adult mouse fibroblasts have similar TGF-beta1 and TGF-beta3 transcriptional regulation of Smad3 and Smad7. This suggests that scarless healing is likely not mediated by different Smad-dependent transcriptional responses to TGF-beta isoforms in the fetal E17 fibroblast.
authors.affiliation: Department of Surgery, Division of Plastic Surgery, Children's Surgical Research Program, Tissue Regeneration Laboratory, Stanford, Calif. 94305-5148, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Colwell
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Krummel
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: H Peter
authors.initials: HP
authors.lastname: Lorenz
mesh_terms: D000367:Age Factors; D000818:Animals; D018929:Cell Culture Techniques; D002921:Cicatrix / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D020033:Protein Isoforms; D015398:Signal Transduction; D051785:Smad Proteins / Q000096:biosynthesis* / Q000235:genetics; D051900:Smad3 Protein / Q000096:biosynthesis / Q000235:genetics; D051906:Smad7 Protein / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D051785:Smad Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; C508961:Tgfb1 protein, mouse; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D055513:Connective Tissue Growth Factor; D003094:Collagen