HEPATIC-FIBROSIS, AN ITOPATHY

被引:2
作者
ROSENBAUM, J
MALLAT, A
MAVIER, P
机构
来源
M S-MEDECINE SCIENCES | 1994年 / 10卷 / 12期
关键词
D O I
10.4267/10608/2563
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hepatic fibrosis complicates most chronic liver diseases. It carries a high morbidity and mortality rate, due to its endpoint, cirrhosis of the liver. The cell type responsible for the major part of fibrosis deposition is the Ito cell. This perisinusoidal cell, involved in retinol metabolism in the normal liver, switches to a myofibroblastic phenotype, proliferates and synthetizes extracellular matrix components during fibrognesis. The mechanisms responsible for this ''activation'' have been studied in detail. A 3-step model of activation has been proposed. In the first step, necrotic hepatocytes initiate Ito cell proliferation by releasing a mitogenic mediator. In the second step, mononuclear cells, activated by the products of hepatocyte lysis, release several cytokines, including transforming growth factor beta 1, that affect the phenotypic modulation of Ito cells into myofibroblasts. Finally, myofibroblastic Ito cells are then able to sustain the activation by secreting multiple cytokines acting through an autocrine/paracrine pathway by themselves. The activation is also influenced by the disruption of the normal extracellular matrix by metalloproteinases secreted by Ito and Kupffer cells. In parallel, the breakdown of the newly synthetized matrix is impaired due to decreased expression of interstitial collagenase together with increased expression of the tissue inhibitor of metalloproteinases-1 in the diseased liver. An adequate treatment for hepatic fibrosis is still lacking. Future research is aiming at several targets : decreasing the activation of Ito cells, stimulating fibrosis degradation and developing profibrogenic cytokines antagonists.
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页码:1245 / 1252
页数:8
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