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基质金属蛋白酶和组织源性金属蛋白酶抑制剂在胎儿及成人皮肤中的差异表达

Differential expression of matrix metalloproteinases and tissue-derived inhibitors of metalloproteinase in fetal and adult skins.

作者信息

Chen Wei, Fu Xiaobing, Ge Shili, Sun Tongzhu, Sheng Zhiyong

机构信息

Key Research Laboratory of Wound Repair, The First Affiliated Hospital, 301th Hospital of Beijing, 100037 Beijing, China.

出版信息

Int J Biochem Cell Biol. 2007;39(5):997-1005. doi: 10.1016/j.biocel.2007.01.023. Epub 2007 Feb 2.

Abstract

Matrix metalloproteinases and their tissue-derived inhibitors determine the architecture of the extracellular matrix. In early gestation, the amount and organization of extracellular matrix may be associated with scarless repair of fetal skin wounds. To elucidate the part of the mechanism(s) underlying the phenotypic transition from scarless to scar-forming healing observed during fetal gestation, the ontogeny of matrix metalloproteinase-2, -9, -14 and their tissue inhibitors was characterized in non-wounded fetal human skin with different gestational ages from 13 to 33 weeks and adult skin using reverse transcriptase-polymerase chain reaction, immunohistochemical staining and western blot protocols. We showed that the levels of gene expressions for matrix metalloproteinase-2, -9, -14 and their endogenous inhibitors were significantly more in late gestational and adult skins than that in early gestational skin. Similar results were noted in terms of protein contents of these enzymes and inhibitors in fetal and adult skins. We concluded that the endogenous matrix metalloproteinase-2, -9, -14 and their endogenous inhibitors might be involved in skin development and in maintenance of cutaneous structure and function. Lower protein contents of tissue-derived inhibitor-1, -2 in early gestational skin might provide a predominantly antiscarring signal while higher protein expression of these two inhibitors might be associated with scar-forming healing in late gestational and adult skins.

摘要

基质金属蛋白酶及其组织来源的抑制剂决定了细胞外基质的结构。在妊娠早期,细胞外基质的数量和组织方式可能与胎儿皮肤伤口的无瘢痕修复有关。为了阐明在胎儿期观察到的从无瘢痕愈合到瘢痕形成愈合的表型转变背后的部分机制,我们采用逆转录聚合酶链反应、免疫组织化学染色和蛋白质印迹法,对13至33周不同胎龄的未受伤胎儿皮肤以及成人皮肤中基质金属蛋白酶-2、-9、-14及其组织抑制剂的个体发生情况进行了表征。我们发现,与妊娠早期皮肤相比,妊娠晚期和成人皮肤中基质金属蛋白酶-2、-9、-14及其内源性抑制剂的基因表达水平显著更高。在胎儿和成人皮肤中这些酶和抑制剂的蛋白质含量方面也观察到了类似结果。我们得出结论,内源性基质金属蛋白酶-2、-9、-14及其内源性抑制剂可能参与皮肤发育以及皮肤结构和功能的维持。妊娠早期皮肤中组织来源抑制剂-1、-2的蛋白质含量较低,这可能提供了主要的抗瘢痕信号,而这两种抑制剂在妊娠晚期和成人皮肤中的较高蛋白质表达可能与瘢痕形成愈合有关。

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