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Hepatic stellate cell behavior during resolution of liver injury

Hepatic stellate cell behavior during resolution of liver injury
Hepatic stellate cell behavior during resolution of liver injury
Acute self-limiting and chronic liver injury are both associated with activation and proliferation of hepatic stellate cells (HSCs). In chronic injury, activated stellate cells are the major source of the collagens that comprise fibrosis and cirrhosis, as well as of the tissue inhibitors of metalloproteinases (TIMPs) which inhibit collagen degradation. Recovery from acute and chronic injury is characterized by apoptosis of activated HSCs, which removes extracellular matrix-producing cells that are also expressing TIMPs, thereby relieving the inhibition of matrix degradation. HSC apoptosis is regulated in progressive injury and counterbalances cell proliferation. Apoptosis probably also represents a default pathway for the HSCs. The survival of activated HSCs in liver injury is dependent on soluble growth factors and cytokines, and on components of the fibrotic matrix. Additionally, stimulation of death receptors expressed on HSCs can precipitate their apoptosis. Our increasing understanding of the process of stellate cell behavior in recovery from injury is likely to be important to the design of antifibrotic therapies.
hepatic stellate cell, apoptosis, death receptor, liver fibrosis, matrix degradation
0272-8087
427-436
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2

Iredale, John P. (2001) Hepatic stellate cell behavior during resolution of liver injury. Seminars in Liver Disease, 21 (3), 427-436. (doi:10.1055/s-2001-17557).

Record type: Article

Abstract

Acute self-limiting and chronic liver injury are both associated with activation and proliferation of hepatic stellate cells (HSCs). In chronic injury, activated stellate cells are the major source of the collagens that comprise fibrosis and cirrhosis, as well as of the tissue inhibitors of metalloproteinases (TIMPs) which inhibit collagen degradation. Recovery from acute and chronic injury is characterized by apoptosis of activated HSCs, which removes extracellular matrix-producing cells that are also expressing TIMPs, thereby relieving the inhibition of matrix degradation. HSC apoptosis is regulated in progressive injury and counterbalances cell proliferation. Apoptosis probably also represents a default pathway for the HSCs. The survival of activated HSCs in liver injury is dependent on soluble growth factors and cytokines, and on components of the fibrotic matrix. Additionally, stimulation of death receptors expressed on HSCs can precipitate their apoptosis. Our increasing understanding of the process of stellate cell behavior in recovery from injury is likely to be important to the design of antifibrotic therapies.

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More information

Published date: 2001
Keywords: hepatic stellate cell, apoptosis, death receptor, liver fibrosis, matrix degradation

Identifiers

Local EPrints ID: 27175
URI: http://eprints.soton.ac.uk/id/eprint/27175
ISSN: 0272-8087
PURE UUID: 882ddba1-97dc-40ea-a82a-8a6a6408a9cc

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Date deposited: 26 Apr 2006
Last modified: 15 Mar 2024 07:16

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Author: John P. Iredale

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