背景:TGF-β在生长和发育中起重要作用,但也参与瘢痕形成和纤维化。这种生长因子的差异在无疤痕的胎儿伤口愈合和成人伤口愈合之间是已知的。尽管如此,该领域的大部分数据来自动物研究或体外研究,因此,关于人类状况的信息是不完整和稀缺的。
目的:本研究的目的是比较未受伤的人胎儿和成人皮肤中的典型TGF-β信号传导。
方法:Q-PCR,免疫组织化学,蛋白质印迹和Luminex测定用于确定基因表达,健康皮肤中蛋白质水平和该途径成分的蛋白质定位。
结果:经典TGF-β途径的所有成分均存在于未受伤的胎儿皮肤中。与成人皮肤相比,胎儿皮肤有不同浓度的TGF-β亚型,有高水平的磷酸化受体Smads,尤其是在表皮,并且几个纤维化相关靶基因的低表达。Further,结果表明,胎儿和成人皮肤的受体内吞过程也可能有所不同。
结论:这项描述性研究表明,基因表达存在差异,胎儿和成人皮肤之间典型TGF-β途径的大多数成分的蛋白质浓度和蛋白质定位。这项研究的发现可以成为进一步研究TGF-β信号传导在无疤痕愈合中的作用的起点。
BACKGROUND: TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce.
OBJECTIVE: The aim of this
study was to compare the canonical TGF-β signaling in unwounded human fetal and adult skin.
METHODS: Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy skin.
RESULTS: All components of the canonical TGF-β pathway were present in unwounded fetal skin. Compared to adult skin, fetal skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and adult skin.
CONCLUSIONS: This descriptive
study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and adult skin. The findings of this
study can be a starting point for further research into the role of TGF-β signaling in scarless healing.