title: Ontogeny of expression of transforming growth factor-beta 1 (TGF-beta 1), TGF-beta 3, and TGF-beta receptors I and II in fetal rat fibroblasts and skin.
abstract: Fetal cutaneous wounds that occur in early gestation heal without scar formation. Although much work has been done to characterize the role of transforming growth factor-beta (TGF-beta) isoforms in the adult wound repair process, their function in fetal scarless wound repair is not well understood. The authors hypothesized that the pattern of expression for TGF-beta isoforms and their receptors may influence the phenotypic transition from scarless to scar-forming repair observed during fetal gestation. Using time-dated fetal Sprague-Dawley rat fibroblasts and unwounded skin at gestational ages 14, 16, 18, and 21 days postcoitum of the scarless (< or =16 days) and scar-forming (>16 days) periods of gestation (term = 21.5 days), the authors analyzed the endogenous messenger RNA (mRNA) levels of TGF-beta 1 and TGF-beta 3 and their signaling receptors TGF-beta-RI and TGF-beta-RII. Northern blot analyses in both fibroblasts and unwounded skin revealed that levels of TGF-beta 1 were not differentially expressed, whereas more TGF-beta 3 mRNA transcript was found in early than in late gestation. Fibroblast expression of TGF-beta-RI showed no substantial differences, whereas expression of TGF-beta-RII increased during gestation. In contrast, expression of both TGF-beta-RI and TGF-beta-RII in unwounded skin showed decreasing levels as a function of gestational age. The differential levels of TGF-beta 1 and TGF-beta 3 suggest that the ratio of these cytokines may provide a predominantly antiscarring or profibrotic signal upon wounding during the scar-free or scar-forming periods of gestation, respectively. Furthermore, lower amounts of the ligand-binding TGF-beta-RII seen in early gestation fibroblasts suggest a decreased ability to perceive ligand during the period of scarless repair.
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hsu
authors.forename: Z M
authors.initials: ZM
authors.lastname: Peled
authors.forename: G S
authors.initials: GS
authors.lastname: Chin
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D005865:Gestational Age; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta; D012867:Skin / Q000196:embryology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3