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剂（TIMP）-1是基质金属蛋白酶活性的重要调节因子，最近我们发现慢性活动性肝病患者血清中TIMP-1水平升高，与肝纤维化的组织学程度相关。为了阐明患病肝脏中 TIMP-1 的变化，我们测量了慢性肝病患者肝组织样本中 TIMP-1 的浓度，并对慢性肝病患者进行了免疫组织化学染色。 TIMP-1。在一些患者中检查了TIMP-1的血清和肝脏水平之间的关系与对照相比，慢性活动性2A型肝炎患者的平均肝脏TIMP-1水平增加了2.9倍。慢性活动性肝炎2B患者为肝硬化患者的4.1倍，但慢性迁延性肝炎患者肝脏TIMP-1水平未见明显升高。门静脉周围坏死、门管炎症、肝纤维化的组织学程度免疫组化检查TIMP-1的定位，TIMP-1主要在肝细胞内染色，慢性活动性肝炎和肝硬化的肝脏中强度更强。与慢性迁延性肝炎患者相比,血清TIMP-1与肝脏TIMP-1水平显着相关,表明血清TIMP-1水平显着相关。可以反映慢性肝病患者肝脏TIMP-1的变化，对肝脏提取物和血浆进行凝胶过滤，结果显示两个样品中TIMP-1的主峰在40 kDa左右被洗脱，表明TIMP-1以TIMP的形式存在。 -1 与可能是 MMP 片段的小蛋白复合。转化生长因子 (TGF) -β1 是参与血浆 TIMP-1 产生的重要细胞因子。 TGF-β1水平与血液中TIMP-1水平呈正相关。综上所述，肝脏TIMP-1浓度随着肝脏疾病的进展而升高，细胞外基质蛋白的降解减少，从而导致肝纤维化的发展较少。