胎儿和出生后机体皮肤内TGF—β_1,TGF-β_3及其受体基因表达变化的比较性研究

A comparative study of expression characteristics of TGF-β_1, TGF-β_3 and their receptors in skin at different developmental stages

目的:探讨转化生长因子-β_1(TGF-β_1),转化生长因子-β_3(TGF-β_3)及其Ⅰ-型受体(TBRⅠ)和Ⅱ-型受体(TBRⅡ)在不同胎龄胎儿的皮肤和出生后机体皮肤组织中表达变化特征及其可能的生物学意义。方法:用病理学技术检测不同发育时期皮肤的结构特征后,提取18例不同胎龄(13～32周)的胎儿皮肤和6例出生后机体皮肤组织的总RNA后,分离mRNA,用RT-PCR方法检测这4种基因在不同组织中的表达变化规律。结果:TGF-β_1,TBRⅠ和TBRⅡ基因在不同妊娠时期的胎儿皮肤和出生后机体皮肤组织中都有表达。在早期妊娠胎儿的皮肤组织中,这3种基因表达较弱,随着胎龄的增加,皮肤组织内这3种基因表达逐渐增强。在出生后机体的皮肤组织中,这些基因的表达量分别为早期妊娠胎儿皮肤的1.3倍、1.3倍和1.2倍,基因表达显著升高(P<0.05)。TGF-β_3基因表达变化规律恰恰相反,在早期妊娠胎儿的皮肤组织中,该基因表达较强,而在出生后机体的皮肤组织中,该基因表达产物的密度值为0.158±0.095,与早期妊娠胎儿皮肤相比显著下降(P<0.01)。结论:TGF-β_1,TGF-β_3及其受体基因在不同发育阶段人皮肤组织内都有表达,显示这些细胞因子与其受体结合后引起的信号通路可能对皮肤的发生、结构功能的维持以及伤后修复十分重要。在早期妊娠胎儿皮肤中TGF-β_1,TBRⅠ和TBRⅡ基因低表达,TGF-β_3基因的高表达可能与胎儿皮肤创面无瘢痕修复密切相关。

To investigate gene expression of transforming growth factor-beta (TGF-β)_1, TGF-β_3, and their receptors (TBR Ⅰ and TBR Ⅱ) in fetal skin at different developmental stages. Skin specimens were ob tained from human fetuses of spontaneous abortion at different gestational ages and postnatal skin. The aim of the study was to explore the potential biological significance of these grouth factors and their recaptors. Methods:Fetal skin from 13-32-week fetuses and postnatal skin(4-16 years old)specimens were collected from patients undergoing plastic surgery. Morphological characteristics of skin at different developmental stages were determined with path ological methods, gene expression of TGF-β_1, TGF-β_3, TBR Ⅰ and TBR Ⅱ in skins at different developmental sta ges was assayed with reverse transcription-polymerase chain reaction (RT-PCR). Results: Gene expressions of TGF-β_1, TGF-β_3, TBR Ⅰ and TBR Ⅱ could all be detected in fetal and postnatal skins. In skins of early gestational fetal (ETPF), gene expressions of TGF-β_1, ,TBR Ⅰ and TBR Ⅱ were weak. Along with advance in gestational age, the gene expressions of these 3 genes in skins became stronger. In late gestational fetal (LTPF) and postnatal skins, the mRNA contents of these 3 genes were significantly increased compared with LTPF skins (P<0.05). On the contrary, the mRNA content of TGF-β_3 was apparently higher in ETPF skins than that of LTPF and post natal skins (P<0.05). Conclusion:The endogenous TGF-β_1, TGF-β_3 and their receptors might be involved in the development of the skin at embryonic stage and in the establishment of cutaneous structure and function, and also in skin wound healing in children under 16 years old. The relatively weak expression of TGF-β_1, TBR Ⅰ and TBR Ⅱ in skin of fetuses at earlier gestational stages might be an important factor to scar-less healing in fetus. The presence of high TGF-β_3 mRNA levels in the fetal skin as compared with postnatal skin may be an additional con tributory factor for the scar free healing observed in fetal skin wound.