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Study for the role of proteoglycans during tissue repair after acute liver injury

蛋白多糖在急性肝损伤组织修复中的作用研究

基本信息

批准号：
05670476
负责人：
KOIDE Norio
金额：
$ 1.22万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670476/
关键词：
Extracellular matrix D-gal liver injury proteoglycan decorin biglycan fibroglycan extracellular matrix syndecan

项目摘要

We investigated the role of proteoglycans (PG) during tissue repair after acute liver injury induced to rats by the administration of D-galactosamine. By immunohistochemical study using anti-heparansulfate antibodies and anti DELTAdi antibodies both heparansulfate-PGs and chondroitin sulfate PGs transiently changed in the early phase of acute liver injury.Heparansulfate-PGs transiently disappeared form hepatocyte at 6h after the initiation of acute liver injury and chondroitinsufate PGs increased in staining bi-phasically ; the early increase was found along sinusoid from 6h to day 3 and the late increase was along fibers appeared in the necrotic area after day 4. Analyzes by northern blotting and in situ hybridization indicated that the late increase of chondroitinsulfate-PGs corresponded to the transcriptional increases of decorin and biglycan, both of which were the member of small chondroitinsulfate/dermatansulfate PGs. The early increase of chondroitinsulfate-PGs was indicated to correspond to the increase of unidentified proteoglycans with molecular weight of 163 kDa and 152 kDa that was identified by anti-DELTAdi antibodies. Such the transient increase of chondroitinsulfate proteoglycans may provide the environment efficient to allow the proliferation, since the mitosis requires cell detachment from the extracellular matrix.While the transiently disappearing heparansulfate-PGs was found by northern blot analysis to be fibroglycan, one of membrane type heparansulfate PGs. It was found by others that fibroglycan was capable to bind hepatocyte growth factor, which was a strong mitogen of hepatocytes. Thus, the disappearance of fibroglycan at an early phase of acute liver injury may provide an environment efficient for the binding of HGF to c-Met, true receptor for HGF,which promote the mitogenic response during tissue repair.

我们研究了蛋白多糖（PG）在d -半乳糖胺诱导大鼠急性肝损伤后组织修复中的作用。通过抗硫酸肝素抗体和抗DELTAdi抗体的免疫组化研究，硫酸肝素-PGs和硫酸软骨素PGs在急性肝损伤早期发生了短暂的变化。急性肝损伤开始后6h，硫酸软骨素-PGs在肝细胞中瞬间消失，硫酸软骨素-PGs双相染色增加；第6h至第3天，早期沿正弦波升高，第4天后，晚期沿坏死区纤维升高。northern blotting和原位杂交分析表明，胰岛素软骨素-PGs的后期增加与decorin和biglycan的转录增加相对应，两者都是小的胰岛素软骨素/皮肤硫酸酯PGs的成员。胰岛素软骨素- pgs的早期增加与抗deltadi抗体鉴定的分子量为163 kDa和152 kDa的未知蛋白聚糖的增加相对应。由于有丝分裂需要细胞脱离细胞外基质，因此胰岛素软骨素蛋白聚糖的短暂增加可能为增殖提供了有效的环境。而瞬时消失的硫酸肝素- pg经northern blot分析为膜型硫酸肝素- pg的一种纤维聚糖。其他人发现纤维聚糖能够结合肝细胞生长因子，肝细胞生长因子是肝细胞的强丝裂原。因此，急性肝损伤早期纤维聚糖的消失可能为HGF与c-Met （HGF的真受体）结合提供了有效的环境，从而促进组织修复过程中的有丝分裂反应。