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（TIMP）-1的组织抑制剂是基质金属蛋白酶活性的重要调节剂。最近，我们证明了慢性活性肝病患者的血清TIMP-1水平升高，与肝纤维化的组织学程度相关。为了阐明陷入困境的生活中TIMP-1的变化，我们测量了来自慢性肝病患者的肝组织样品中的TIMP-1浓度。我们对TIMP-1进行了免疫组织化学染色。在某些患者中检查了血清和肝脏水平之间的关系。与对照组相比，慢性肝炎2A患者的平均肝TIMP-1水平增加了2.2倍，慢性活性丙型肝炎2B患者2.9倍，肝硬化患者4.1倍，但在慢性持续性肝炎患者中未观察到显着增加。肝TIMP-1水平与周围坏死的组织学程度密切相关，…更多的门静脉感染和肝纤维化。当对TIMP-1的定位进行了免疫组织化学检查时，TIMP-1主要在肝细胞中染色，并且在慢性活性肝炎和肝硬化患者生活中的强度比在慢性持续性肝炎患者的生活中更强。血清TIMP-1和肝TIMP-1水平显着相关，表明血清TIMP-1可以反映慢性肝病患者肝脏TIMP-1的变化。肝脏提取物和血浆的gelfiltrattion表明，这两个样品中TIMP-1的主要峰值在40 kDa左右洗脱，表明TIMP-1与TIMP-1的存在为TIMP-1与小蛋白相络合，这可能是MMP.Transform.transform.transform的生长因子（TGF）的片段-BETA1 -BETA1-BETA1与Timp-1的生产中的重要细胞菌相关。等离子体TGF-BETA1水平与TIMP-1 IN结论的血液水平呈正相关，TIMP-1浓度随肝病的进展而增加，在肝病的进展中，细胞外基质蛋白的降解降低，导致肝纤维化的发展。较少的