胎儿和出生后机体皮肤内p38MAPK及MAPKKs基因表达变化的比较性研究

GENE EXPRESSION OF p38 MITOGEN-ACTIVATED PROTEIN KINASE AND ITS MAPKKs IN SKIN AT DIFFERENT DEVELOPMENTAL STAGES AND ITS POSSIBLE BIOLOGICAL SIGNIFICANCE

目的 探讨p38丝裂素活化蛋白激酶(p38mitogen- activated protein kinase,p38MAPK)及其上游信号分子MAPKKs(mkk3和mkk6 )基因,在不同胎龄胎儿皮肤和出生后机体皮肤组织中表达的变化,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(作为对照)的总RNA,分离m RNA,用逆转录-聚合酶链反应(reverse transcription- polymerasechain reaction,RT- PCR)方法检测3种基因在不同组织中的表达规律。 结果 p38MAPK,m kk3和mkk6基因在不同发育阶段的皮肤组织中都有表达。在早期妊娠胎儿的皮肤组织中,这三种基因表达较强,随着胎儿的生长发育,皮肤组织内这三种基因表达逐渐减弱。在出生后机体的皮肤细胞中,p38MAPK、mkk3和mkk6基因的表达量分别为妊娠早期皮肤的39.6 %、6 3.5 %和5 4 .5 % ,明显减弱(P<0 .0 1)。 结论 p38MAPK、mkk3和mkk6基因在不同发育阶段人皮肤组织内都有表达,显示细胞外信号引起的p38MAPK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p38MAPK及其上游信号分子MAPKKs基因的高表达可能是胎儿皮肤组织细胞快速增殖、皮肤创面无瘢痕愈合的机制之一。

Objective To investigate the gene expression of p38 mitogen-activated protein kinase (p38MAPK) and its upstream signaling molecule (mkk3 and mkk6) in fetal skin at different developmental stages and postnatal skin and its potential biological significance. Methods The fetal skin biopsies were obtained from human embryo of spontaneous abortion at gestational ages from 13 to 32 weeks and postnatal skin specimens were collected from patients(4-16 years) undergoing plastic surgery. After the morphological characteristics of skins at different developmental stages were detected with pathological methods, the gene expressions of p38MAPK, mkk3 and mkk6 in skins were examined with reverse transcription-polymerase chain reaction analysis (RT-PCR). Results The gene expressions of p38MAPK, mkk3 and mkk6 could all be detected in fetal and postnatal skins. In fetal skins, these 3 genes were strongly expressed. Along with fetal growth and development, the gene expressions of p38MAPK and its upstream signaling molecules were faded gradually. In postnatal skin, the mRNA contents of these 3 genes were significantly decreased in comparison with those in fetal skin ( P <0.01). Conclusion p38 MAPK mediated signal pathways might be involved in the skin development at embryonic stage and in the determination of cutaneous structure and function, and also in wound healing at postnatal stage. The relative increment of these gene transcription in younger fetal skin might be one of the reasons why cutaneous cells proliferate rapidly and the wounds heal without scar.