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Elucidation of the mechanism of scarless wound healing and identification of its master gene

阐明无疤痕伤口愈合机制及其主基因的鉴定

基本信息

批准号：
17591153
负责人：
KON Atsushi
金额：
$ 2.07万
依托单位：
Aomori University of Health and Welfare (2007)Hirosaki University (2005-2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591153/
关键词：
scarless wound healing tvoe VII collagen hvaluronan 遺伝子再生糖鎖創傷治癒皮膚

项目摘要

Previous our studies have demonstrated that hyaluronan is one of important factors for scarless wound healing mechanism. In order to investigate its more details, we first analyzed gene expression in the fetal mouse skin, which scarless wound healing is observed, by serial analysis gene expression (SAGE) techniques. SAGE analyses revealed that over forty kinds of specific genes were detected. The genes for hyaluronan synthase (HAS), type VII collagen, and fibromodulin were upregulated, whereas HOX and PRX families, and TGF-beta genes were down regulated in dermal fibroblasts of scarless wound healing mice. Furthermore, addition of hyaluronan in dermal fibroblasts of adult mice, in which scarless wound healing,are not observed, resulted in similar expression pattern of scarless wound healing specific genes. These resulted suggested that treatment with hyaluronan may induce scarless wound healing mechanism in adult dermal fibroblasts. However, introductions the expression of each gene or its recombinant protein into the wounds of adult mice skin did not disappear scar formation. Therefore, each gene identified in these studies was not master gene of scarless wound healing. On the other hands, treatment of dermal fibroblasts of adult mice with 4-methylumbelliferon (MU), a hyaluronan synthase suppressor, resulted in opposite expression pattern of scarless wound healing specific genes. Oral administration of MU in adult mice caused severe scar formation. Furthermore, dryness and fragility of the skin were also observed, suggesting these mice are useful tools for investigating not only the molecular mechanism of scarless wound healing but also skin aging.

我们前期的研究表明，透明质酸是无疤痕伤口愈合机制的重要因素之一。为了研究其更多细节，我们首先通过系列分析基因表达（SAGE）技术分析了胎儿小鼠皮肤中的基因表达，观察到无疤痕伤口愈合。 SAGE 分析表明检测到了四十多种特定基因。在无疤痕伤口愈合小鼠的真皮成纤维细胞中，透明质酸合酶（HAS）、VII型胶原蛋白和纤维调节蛋白基因上调，而HOX和PRX家族以及TGF-β基因下调。此外，在未观察到无疤痕伤口愈合的成年小鼠的真皮成纤维细胞中添加透明质酸，导致无疤痕伤口愈合特异性基因的相似表达模式。这些结果表明，透明质酸治疗可能会诱导成人真皮成纤维细胞的无疤痕伤口愈合机制。然而，将每种基因或其重组蛋白的表达引入成年小鼠皮肤的伤口中并没有消除疤痕形成。因此，这些研究中鉴定的每个基因都不是无疤痕伤口愈合的主控基因。另一方面，用透明质酸合酶抑制剂 4-甲基伞形酮 (MU) 处理成年小鼠的真皮成纤维细胞，导致无疤痕伤口愈合特定基因的相反表达模式。成年小鼠口服 MU 会导致严重的疤痕形成。此外，还观察到皮肤干燥和脆弱，这表明这些小鼠不仅是研究无疤痕伤口愈合的分子机制，而且是研究皮肤老化的有用工具。