成纤维细胞生长因子-10及其受体对胎儿皮肤附件形成的诱导作用

The induction effects of FGF-10 and its receptors on the formation of fatal skin appendage

目的:探讨成纤维细胞生长因子-10(FGF10)及其受体(FGFR2b 或 Bek)在胎儿皮肤附件(SA)形成中的表达特征及其生物学意义。方法:对130块分别来自26例不同胎龄(EGA 8～31周)胎儿,5个不同部位(头、下颌、耳垂、肩和胸骨柄)的皮肤标本,采用病理学、免疫组化方法和计算机图像扫描技术检测 FGF10、Bek、细胞角蛋白-19(CKl9)、Bcl-2和细胞增殖核抗原(PCNA)在胎儿皮肤组织的表达水平。结果:除 EGA8周胎儿缺乏典型的皮肤组织学结构和 FGF10和 Bek 蛋白表达外,所有蛋白在 E11周以后的皮肤内都有阳性表达。在EGA11周,表皮下成团分布的间质细胞过表达 FGF10、PCNA 和 Bcl-2,表皮细胞和周皮细胞则所有蛋白均呈强阳性表达;在 EGA13周时表皮细胞局灶性增殖形成 SA 胚芽,并逐渐向真皮内生长、分化和迁移;在 EGA11～31周的皮肤组织内,真皮内问质细胞表达 FGF10、PCNA 和 Bcl-2以及 SA 上皮细胞表达 FGF10、Bek、PCNA、CK19和 Bcl-2蛋白呈现与生长发育同步的表达特征,但单个细胞表达的平均光密度(A)值则随胎龄增加而逐渐下降(P<0.05～0.001)。结论:间质细胞旁分泌的 FGF10与上皮细胞膜 Bek 特异性结合,是诱导胚胎 SA 上皮细胞生长及其形态发生的重要信号,但有关 SA 的形成部位和种类及其与 FGF10蛋白表达的相互关系仍有待深入研究。

Objective:To investigate the expression of fihroblast growth factor-10 (FGF-10)as well as its receptors (FGFR2b or Bek)in fetal skin and their effeets on the formation of fetal skin appendage (SA).Methods:130 skin specimens were obtained from 5 different sites (head,lower jaw,ear lobe,shoulder and presternal region)of 26 fetuses with different estimated gestational age (EGA 8—31w).Histologieal examination,immunohistochemistry staining (double-labeled)with antibodies of anti-human FGF-10,anti-Bek,anti-cytokeratin (CK19),anti-Bcl-2 and anti-proliferating cell nuclear antigen (PCNA),and computer image scanning were used to detect the expres- sion levels of those proteins in fetal skin tissues.Results:In EGA 8w-fetal skin,typical histological structure was lacking and expression of FGF-10 and Bek protein were negative,while these proteins were positively expressed after EGAllw.At EGAllw,FGF10,PCNA and Bcl-2 were over-expressed in clustered interstitial eells under epidermis,while all those proteins were strongly positive in epidermal cells and perieytes.In EGA13w-fetal skin, epidermal cells formed SA plumule(anlage)through local proliferation,differentiation and migration towards der- mis.In the skin of EGA11--13w fetuses,the expressions of FGF-10,PCNA and Bel-2 in interstitial cells in der- mis and the expressions of FGF-10,Bek,PCNA,CK19 and Bel-2 in epithelial cells in SA were synchronous with growth and development of fetuses.Along with the increase in gestational age,the values of average light density expressed in a single cell were decreased gradually (P<0,05—0.001).Conclusions:The specific binding of FGF- 10 secreted from interstitial cells to Bek on the membrane of expressed epithelial cells might be an important signal for the induction of the proliferation and morphogenesis.of embryonic SA epithelial ceils,but the site of formation and types of SA,and the relationship between them and FGF-10 expression still need further investigation.