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Tissue inhibitor of metalloproteinases-1 in chronic liver disease.

慢性肝病中金属蛋白酶-1 的组织抑制剂。

基本信息

批准号：
06670553
负责人：
MURAWAKI Yoshikazu
金额：
$ 1.34万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06670553/
关键词：
Liver disease TIMP 慢性肝疾患 TIMP-1

项目摘要

Tissue inhibitor of metalloproteinases (TIMP) -1 is an important regulator of matrix metalloproteinase activity. Recently, we have demonstrated that the serum levels of TIMP-1 are increased in patients with chronic active liver disease, correlating with the histological degree of liver fibrosis. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. We carried out an immunohistochemical staining for TIMP-1. The relationship between serum and liver levels of TIMP-1 was examined in some patients. As compared with the controls, the mean liver TIMP-1 level was increased 2.2-fold in chronic active hepatitis 2A patients, 2.9-fold in chronic active hepatitis 2B patients and 4.1-fold in liver cirrhosis patients, but no significant increase was observed among chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, … More portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease. Gelfiltrattion of liver extract and plasma showed that the major peak of TIMP-1 in both samples was eluted at around 40 kDa, indicating that TIMP-1 is present as TIMP-1 complexed with a small protein which is probably a fragment of MMP.Transforming growth factor (TGF) -beta1 is an important cytokine involved in the production of TIMP-1. Plasma TGF-beta1 levels were positively correlated with blood levels of TIMP-1In conclusion, the liver TIMP-1 concentration increased with the progress of liver disease, where the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis. Less

金属蛋白酶组织抑制因子-1(TIMP-1)是基质金属蛋白酶活性的重要调节因子。近年来，我们发现慢性活动性肝病患者血清TIMP-1水平升高，且与肝纤维化程度呈正相关。为了阐明TIMP-1在病变肝脏中的变化，我们测量了慢性肝病患者肝组织中TIMP-1的浓度。对TIMP-1进行免疫组织化学染色。对部分患者血清和肝脏TIMP-1水平的关系进行了研究。与对照组相比，慢性活动性肝炎患者肝组织TIMP-1水平升高2.2倍，2B型肝炎患者升高2.9倍，肝硬化组升高4.1倍，而慢性迁延性肝炎患者肝组织TIMP-1水平无明显升高。肝组织中TIMP-1水平与门静脉周围坏死、…的组织学分级密切相关更多的门脉炎症和肝纤维化。免疫组织化学检测TIMP-1的定位时，TIMP-1主要表达于肝细胞，慢性活动性肝炎和肝硬变患者的肝脏TIMP-1表达强度高于慢性迁延性肝炎患者。血清TIMP-1与肝组织TIMP-1水平呈显著正相关，提示血清TIMP-1可反映慢性肝病患者肝组织TIMP-1的变化。肝提取液和血浆的凝胶过滤显示，TIMP-1的主峰在40 kDa左右洗脱，表明TIMP-1以TIMP-1的形式存在，可能是MMP的一个片段。转化生长因子-β1是参与TIMP-1产生的重要细胞因子。血浆TIMP-1水平与血清TIMP-1水平呈正相关。结论：肝脏TIMP-1浓度随肝病进展而升高，细胞外基质蛋白降解减少，导致肝纤维化的发生。较少