Morphological characterization of liver fibrogenesis in animal models with genetically modulated TGF-beta signal transduction
type: CreativeWork
description: Production of fibrous scar tissue in the liver is a normal response to injuries. In fibrosis this healing process is disturbed. Liver fibrosis is defined as the accumulation this fibrous scar tissue in the liver. After hepatocyte damage due to e.g. viral infection, heavy alcohol consumption, toxins or trauma, the immune system is activated and the cell repair process of the liver is induced. Injury or death (necrosis) of hepatocytes further stimulates inflammatory immune cells to release cytokines, growth factors, like TGF-beta activating hepatic stellate cells (HSCs) to produce collagen, glycoproteins (such as fibronectin) and proteoglycans. Activatied HSCs differentiate into myofibroblasts expressing alpha-smooth muscle actin (alpha SMA) which are deposited in the liver to form the extracellular matrix (ECM). At the same time, the process of breaking down or degrading collagen is impaired. In a healthy liver, synthesis (fibrogenesis) and degradation (fibrolysis) of matrix tissue are in balance. Fibrosis occurs when scar tissue is generated in excess and faster than it is degraded and removed from the liver. TGF-beta is known to play a central role in regulation of the production, degradation, and accumulation of ECM proteins and that, as a consequence, it may play a pivotal role in the fibroproliferative changes that follow tissue damage in many vital organs, including liver, lung, kidney, skin, heart, and arterial wall.(Massague, J. 1990). Therefore numerous antifibrotic strategies aim to block action of this cytokine or reduce its synthesis. TGF-beta superfamily members bind to serine/threonine kinase receptors. expressing on surface of a variety of cells e.g. hepatocytes and HSCs. TGF-beta receptors comprise two structurally similar subfamilies, the type I and type II receptors, both with small cysteine rich extracellular regions and intracellular portions consisting mainly of their kinase domains. To transmit a signal, type II and type I receptors act in seque…
abstract: Production of fibrous scar tissue in the liver is a normal response to injuries. In fibrosis this healing process is disturbed. Liver fibrosis is defined as the accumulation this fibrous scar tissue in the liver. After hepatocyte damage due to e.g. viral infection, heavy alcohol consumption, toxins or trauma, the immune system is activated and the cell repair process of the liver is induced. Injury or death (necrosis) of hepatocytes further stimulates inflammatory immune cells to release cytokines, growth factors, like TGF-beta activating hepatic stellate cells (HSCs) to produce collagen, glycoproteins (such as fibronectin) and proteoglycans. Activatied HSCs differentiate into myofibroblasts expressing alpha-smooth muscle actin (alpha SMA) which are deposited in the liver to form the extracellular matrix (ECM). At the same time, the process of breaking down or degrading collagen is impaired. In a healthy liver, synthesis (fibrogenesis) and degradation (fibrolysis) of matrix tissue are in balance. Fibrosis occurs when scar tissue is generated in excess and faster than it is degraded and removed from the liver. TGF-beta is known to play a central role in regulation of the production, degradation, and accumulation of ECM proteins and that, as a consequence, it may play a pivotal role in the fibroproliferative changes that follow tissue damage in many vital organs, including liver, lung, kidney, skin, heart, and arterial wall.(Massague, J. 1990). Therefore numerous antifibrotic strategies aim to block action of this cytokine or reduce its synthesis. TGF-beta superfamily members bind to serine/threonine kinase receptors. expressing on surface of a variety of cells e.g. hepatocytes and HSCs. TGF-beta receptors comprise two structurally similar subfamilies, the type I and type II receptors, both with small cysteine rich extracellular regions and intracellular portions consisting mainly of their kinase domains. To transmit a signal, type II and type I receptors act in seque…
author: Sarkhaei, Jafar Hamzavi
language: eng
keywords: info:eu-repo/classification/ddc/570, Leberfibrose, TGF-beta, Smad7, HCS, ECM, Biowissenschaften, Biologie, liver fibrosis
date published: 2007
date modified: 2026-07-30T19:43:19Z
provider: RWTH Aachen University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Publikationsserver der RWTH Aachen University