Regulation of hepatic stellate cell proliferation and collagen synthesis by proteinase-activated receptors
Regulation of hepatic stellate cell proliferation and collagen synthesis by proteinase-activated receptors
Background/Aims: Thrombin and MC tryptase, which are agonists for proteinase-activated receptors-1 and -2, respectively, are both increased in injured liver. We have examined if rat stellate cells express these receptors and if receptor agonists influence stellate cell activation.
Methods: Expression of mRNA for proteinase activated receptors-1 and -2 were examined by RT-PCR and Northern blotting in lysates of cultured stellate cells and receptor protein examined by Western blotting. The effects of receptor agonists on cell proliferation and collagen synthesis were examined by 3H-thymidine and 3H-proline incorporation assays, respectively.
Results: Rat stellate cells activated by culture on plastic showed a progressive increase in expression of proteinase-activated receptor-1 and -2 mRNA and proteinase-activated receptor-2 protein as they transformed to a myofibroblastic phenotype. Proteinase-activated receptor-1 agonists thrombin and the peptide SFFLRN, and proteinase-activated receptor-2 agonists tryptase and the peptide SLIGRL induced stellate cell proliferation and the rapid phosphorylation of 44 and 42 kDa mitogen-activated protein kinases. PD98059, an inhibitor of these kinases, inhibited this proliferative response. Both tryptase and SLIGRL increased collagen secretion by stellate cells.
Conclusions: This study indicates that the natural proteinase-activated receptor agonists thrombin and MC tryptase might sustain liver fibrosis by promoting stellate cell proliferation and collagen synthesis.
hepatic stellate cell, proteinase-activated receptor, collagen, fibrosis, mast cell, pryptase, thrombin
362-369
Gaca, Marianna D. A.
c96f2d08-9c43-4198-9c6b-b9c86f6729f8
Zhou, Xiaoying
52423958-8092-4391-9e96-e7422c12e1b9
Benyon, R. Christopher
6efa9278-56e6-47ec-9854-78afd98dd4c9
2002
Gaca, Marianna D. A.
c96f2d08-9c43-4198-9c6b-b9c86f6729f8
Zhou, Xiaoying
52423958-8092-4391-9e96-e7422c12e1b9
Benyon, R. Christopher
6efa9278-56e6-47ec-9854-78afd98dd4c9
Gaca, Marianna D. A., Zhou, Xiaoying and Benyon, R. Christopher
(2002)
Regulation of hepatic stellate cell proliferation and collagen synthesis by proteinase-activated receptors.
Journal of Hepatology, 36 (3), .
(doi:10.1016/S0168-8278(01)00285-9).
Abstract
Background/Aims: Thrombin and MC tryptase, which are agonists for proteinase-activated receptors-1 and -2, respectively, are both increased in injured liver. We have examined if rat stellate cells express these receptors and if receptor agonists influence stellate cell activation.
Methods: Expression of mRNA for proteinase activated receptors-1 and -2 were examined by RT-PCR and Northern blotting in lysates of cultured stellate cells and receptor protein examined by Western blotting. The effects of receptor agonists on cell proliferation and collagen synthesis were examined by 3H-thymidine and 3H-proline incorporation assays, respectively.
Results: Rat stellate cells activated by culture on plastic showed a progressive increase in expression of proteinase-activated receptor-1 and -2 mRNA and proteinase-activated receptor-2 protein as they transformed to a myofibroblastic phenotype. Proteinase-activated receptor-1 agonists thrombin and the peptide SFFLRN, and proteinase-activated receptor-2 agonists tryptase and the peptide SLIGRL induced stellate cell proliferation and the rapid phosphorylation of 44 and 42 kDa mitogen-activated protein kinases. PD98059, an inhibitor of these kinases, inhibited this proliferative response. Both tryptase and SLIGRL increased collagen secretion by stellate cells.
Conclusions: This study indicates that the natural proteinase-activated receptor agonists thrombin and MC tryptase might sustain liver fibrosis by promoting stellate cell proliferation and collagen synthesis.
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Published date: 2002
Keywords:
hepatic stellate cell, proteinase-activated receptor, collagen, fibrosis, mast cell, pryptase, thrombin
Identifiers
Local EPrints ID: 27065
URI: http://eprints.soton.ac.uk/id/eprint/27065
ISSN: 0168-8278
PURE UUID: 61273dc0-94f9-4bbf-8828-ffdbfff4018f
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Date deposited: 28 Apr 2006
Last modified: 15 Mar 2024 07:15
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Author:
Marianna D. A. Gaca
Author:
Xiaoying Zhou
Author:
R. Christopher Benyon
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