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

Fetal cutaneous wounds that occur in early gestation heal without scar form ation. Although much work has been done to characterize the role of transfo rming growth factor-beta (TGF-beta) isoforms in the adult wound repair proc ess, their function in fetal scarless wound repair is not well understood. The authors hypothesized that the pattern of expression for TGF-beta isofor ms and their receptors may influence the phenotypic transition from scarles s 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 (less than or equal to 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-b eta1 and TGF-beta3 and their signaling receptors TGF-beta -RI and TGF-beta -RII. Northern blot analyses in both fibroblasts and unwounded skill reveal ed that levels of TGF-beta1 were not differentially expressed, whereas more TGF-beta1 mRNA transcript was found in early than in late gestation. Fibro blast expression of TGF-beta -RI showed no substantial differences, whereas expression of TGF-beta -RII increased during gestation. In contrast, expre ssion of both TGF-beta -RI and TGF-beta -RII in unwounded skin showed decre asing levels as a function of gestational age. The differential levels of T GF-beta1 and TGF-beta3 suggest that the ratio of these cytokines may provid e a predominantly antiscarring or profibrotic signal upon wounding during t he scar-free or scar-forming periods of gestation, respectively. Furthermor e, lower amounts of the ligand-binding TGF-beta -RII seen in early gestatio n fibroblasts suggest a decreased ability to perceive ligand during the per iod of scarless repair.