The ontogeny of scarless healing II: EGF and PDGF-B gene expression in fetal rat skin and fibroblasts as a function of gestational age

Twenty years ago, surgeons noted the ability of early-gestation fetal skin to heal in a scarless manner. Since that time, numerous investigators have attempted to elucidate the mechanisms behind this phenomenon. As a result o f this effort, it is now well established that many animals undergo a trans ition late in development from scarless cutaneous healing to a scar-forming , adultlike phenotype. The authors have been interested in the role played by cytokines known to be involved in the adult wound-healing process and ho w they relate to scarless repair. They therefore asked the following questi on: Are genes for epidermal growth factor (EGF) and platelet-derived growth factor-B (PDGF-B) expressed differentially as a function of gestational ag e in fetal rat skin and dermal fibroblasts? To answer this question, skin f rom fetal Sprague-Daw[ey rats (N = 56) at time points that represented both the scarless and scar-forming periods of rat gestation was harvested. In a ddition, fibroblasts derived from fetal rat skin were cultured in vitro at similar times. These cells were expanded in culture and, when confluent, to tal ribonucleic acid from both fibroblasts and whole skin was extracted and subjected to Northern blot analysis with probes for EGF and PDGF-B. Result s demonstrated that neither EGF nor PDGF-B gene expression changed markedly as a function of gestational age in fetal fibroblasts alone. In whole skin , however, both EGF and PDGF-B demonstrated a marked decrease in gene expre ssion with increasing gestational age. Furthermore, the most striking decre ase in gene expression for both cytokines came between 16 and 18 days of ge station-the transition point between scarless and scar-forming repair in th e fetal rat. These data suggest that EGF and PDGF may play a role in the me chanism of scarless cutaneous repair. Moreover, it appears that fetal fibro blasts are not the cell type responsible for this differential gene express ion. These results raise questions about the unique cytokine milieu likely to be present during the time of scarless healing and the cells that ultima tely guide the mechanisms leading to skin regeneration.