Peled Z M, Rhee S J, Hsu M, Chang J, Krummel T M, Longaker M T
Children's Surgical Research Program, Stanford University School of Medicine, CA 94305-5148, USA.
Ann Plast Surg. 2001 Oct;47(4):417-24. doi: 10.1097/00000637-200110000-00010.
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 of this effort, it is now well established that many animals undergo a transition 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 how they relate to scarless repair. They therefore asked the following question: Are genes for epidermal growth factor (EGF) and platelet-derived growth factor-B (PDGF-B) expressed differentially as a function of gestational age in fetal rat skin and dermal fibroblasts? To answer this question, skin from fetal Sprague-Dawley rats (N = 56) at time points that represented both the scarless and scar-forming periods of rat gestation was harvested. In addition, fibroblasts derived from fetal rat skin were cultured in vitro at similar times. These cells were expanded in culture and, when confluent, total ribonucleic acid from both fibroblasts and whole skin was extracted and subjected to Northern blot analysis with probes for EGF and PDGF-B. Results 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 expression with increasing gestational age. Furthermore, the most striking decrease in gene expression for both cytokines came between 16 and 18 days of gestation-the transition point between scarless and scar-forming repair in the fetal rat. These data suggest that EGF and PDGF may play a role in the mechanism of scarless cutaneous repair. Moreover, it appears that fetal fibroblasts are not the cell type responsible for this differential gene expression. These results raise questions about the unique cytokine milieu likely to be present during the time of scarless healing and the cells that ultimately guide the mechanisms leading to skin regeneration.
二十年前，外科医生注意到妊娠早期胎儿皮肤能够以无瘢痕的方式愈合。从那时起，众多研究人员试图阐明这一现象背后的机制。经过这项努力，现已明确许多动物在发育后期会经历从无瘢痕皮肤愈合到形成瘢痕的、类似成体表型的转变。作者一直对已知参与成人伤口愈合过程的细胞因子所起的作用以及它们与无瘢痕修复的关系感兴趣。因此，他们提出了以下问题：在胎鼠皮肤和真皮成纤维细胞中，表皮生长因子（EGF）和血小板衍生生长因子-B（PDGF-B）的基因表达是否会随着胎龄的变化而出现差异？为了回答这个问题，收集了处于代表大鼠妊娠无瘢痕期和瘢痕形成期的时间点的胎龄Sprague-Dawley大鼠（N = 56）的皮肤。此外，在相似时间对源自胎鼠皮肤的成纤维细胞进行体外培养。这些细胞在培养中扩增，汇合后，提取成纤维细胞和全皮肤的总核糖核酸，并用针对EGF和PDGF-B的探针进行Northern印迹分析。结果表明，仅在胎龄成纤维细胞中，EGF和PDGF-B基因表达均未随胎龄发生明显变化。然而，在全皮肤中，EGF和PDGF-B的基因表达均随着胎龄增加而显著降低。此外，两种细胞因子基因表达最显著的降低发生在妊娠16至18天之间——这是胎鼠无瘢痕修复和瘢痕形成修复的转折点。这些数据表明，EGF和PDGF可能在无瘢痕皮肤修复机制中发挥作用。此外，似乎胎龄成纤维细胞不是负责这种差异基因表达的细胞类型。这些结果引发了关于无瘢痕愈合期间可能存在的独特细胞因子环境以及最终引导皮肤再生机制的细胞的疑问。
