目的:研究基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)及其组织抑制因子(TIMP-2)在不同胎龄的胎儿皮肤中表达的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胎儿皮肤的结构特征后,提取18例不同胎龄(13~33周)的胎儿皮肤总RNA后,分离mRNA,用RT—PCR方法检测这3种基因在不同组织中的表达变化规律。结果:MMP-9、MMP-2和TIMP-2基因在不同发育时期的胎儿皮肤组织中的表达变化规律相似。在早期妊娠胎儿皮肤中,这3种基因表达较弱,随着胎儿生长发育,MMP-9,MMP-2和TIMP-2基因表达逐渐增强,妊娠晚期的皮肤组织内,这3种基因表达产物的灰密度比值分别是妊娠早期的8.8、2.4和3.1倍,基因表达水平显著升高(P〈0.05)。结论:MMP-9,2和TIMP-2对皮肤的生长发育、结构功能的维持以及创面修复具有重要的调节作用。妊娠早期,TIMP-2基因低表达可能与胎儿皮肤创面无瘢痕愈合相关,而妊娠晚期皮肤中TIMP-2基因表达增强可能是创面愈合后形成瘢痕的机制之一。
Objective: To explore the change in gene expression in matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in fetal skin at different developmental stages, and their potential biological significances. Methods: Human fetal skin biopsies were obtained from spontaneous abortion at different gestational ages from 13--33 weeks. After morphological characteristics of skin at different developmental stages were detected with routine pathological methods, gene expression of MMP-9, MMP-2 and TIMP-2 was respectively determined with reverse transcription-polymerase chain reaction(RT-PCR). Results: The changeable tendencies of gene expression of MMP-9, MMP-2 and TIMP-2 were similar in different skin specimens at various developmental stages. In early gestational fetal skin, genes of MMP-9, MMP-2 and TIMP-2 were weakly expressed. Along with fetal skin development, the expression levels of these 3 genes were progressively increased. In late gestational skin, the expression levels of MMP-9, MMP-2 and TIMP-2 were significantly increased (P〈0.05), while the gray ratios of transcripts of these 3 genes were 8.8, 2.4 and 3.1 times of those in early gestational skin respectively. Conclusion: The endogenous MMP-9, 2 and TIMP-2 might be involved in fetal skin development and in maintenance of cutaneous structure and function, and also in wound healing. Lower gene expression of TIMP-2 in early gestational skin may be the underlying mechanism of the scar-free healing, while higher gene expression of TIMP-2 might be associated with scar-forming healing in late gestational skin.