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皮膚の創傷治癒過程における癌関連遺伝子の動態とその法医病理学的応用

皮肤伤口愈合过程中癌相关基因的动态及其法医病理学应用

基本信息

批准号：
13470101
负责人：
大島徹
金额：
$ 9.22万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

皮膚創傷治癒過程は,炎症期,増殖期,成熟期と3つの時期に大別される生体防御反応である.この過程に関与する様々な細胞は,細胞表面分子を介した細胞間相互作用によって制御されている.細胞表面のガラクトース糖鎖は細胞間相互作用に重要な役割を果たしていると考えられているが,未だ詳細な検討はなされていない.本研究では,皮膚創傷治癒過程におけるガラクトース糖鎖の生物学的意義の解明を目的として,β-1,4-ガラクトース転移酵素(GalT)-I欠損(KO)マウス及びヘテロマウスの背部に皮膚欠損創を作製し,創傷治癒に関与する種々の因子についての経時的測定を行い,治癒の程度を比較検討した.ヘテロマウスに比べGalT-I KOマウスは創の閉鎖率,肉芽組織内における血管内皮細胞占有率,再上皮化が,各々有意に減少していた.さらに,損傷部におけるコラーゲン量が有意に減少しており,それらに関与する分子(TGF-β1,CTGF,COL1A1)並びに血管新生に関与するVEGFの発現が,各々有意に減少していた.損傷部における炎症の様態については,ヘテロマウスに比べGalT-I KOマウスでは,マクロファージ数及びケモカイン(MCP-1,MIP-1α,MIP-2)の発現が,各々有意に減少していた.以上から,コントロールマウスに比べGalT-I KOマウスは炎症反応の減弱が認められ,また,組織修復や血管新生に関与する遺伝子発現の減少が認められた.その結果として,GalT-I KOマウスでは皮膚創傷治癒が遅延したものと判断された.GalT-Iはセレクチンのリガンド糖鎖であるシアリルLexの生合成に関与していることから,GalT-I KOマウスでは創部へ白血球浸潤細胞数の減少が生じ,その結果,それら細胞群が分泌する増殖因子等の減少が生じたことで治癒が遅延したと考えられる.

During the treatment process of dermatosis, inflammation, gonorrhea, and maturity, there are significant differences in the prevention and treatment of anti-inflammatory diseases. During the process and in the cell, the molecules on the cell surface are involved in the intercellular interaction, so as to control the cell cycle. The intercellular interaction is very important in terms of cell surface temperature, glucose and glucose intercellular intercellular interaction. The purpose of this study is to understand the meaning of glucose metabolism in the process of skin treatment. The purpose of this study is to understand the meaning of glucose biology. in this study, the process of skin treatment is related to the meaning of glucose biology. the purpose of this study is to understand the meaning of glucose biology. the purpose of this study is to understand the meaning of glucose biology. the purpose of this study is to understand the meaning of glucose biologics. the purpose of this study is to understand the meaning of glucose biology. in this study, the process of skin treatment is related to the meaning of glucose biology. the purpose of this study is to understand the meaning of glucose biology. the purpose of this study is to understand the meaning of glucose biology. the purpose of this study is to understand the meaning of glucose biology. The degree of treatment is better than that of treatment. The percentage of endothelial cells in granulation tissue and epithelialization was significantly lower than that in GalT-I KO tissue. We are interested in the detection of TGF- β 1 (CTGF,COL1A1) and angiogenesis and the presence of VEGF. The number of patients with inflammation was higher than that of GalT-I KO patients, the number of patients with inflammation and the number of patients with inflammation (MCP-1,MIP-1 α, MIP-2) were significantly lower. The results of this study show that there are fewer signs of angiogenesis in the tissue repair system than in the GalT-I KO group, where the inflammatory response is weaker than that in the tissue. The results showed that the treatment of GalT-I KO was delayed and the number of white blood cells was reduced. The results showed that there was a decrease in the number of white blood cells in the part of GalT-I KO, and the results showed that there was no significant difference in the number of white blood cells between the two groups. The results showed that there were significant differences in the synthesis of Lex, the number of white blood cells, the number of white blood cells and the number of white blood cells. The cell population secretes reproductive factors and so on. There is no significant difference in treatment.