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Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo

Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo
Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo
Background: Following liver injury, hepatic stellate cells (HSC) transform into myofibroblast-like cells (activation) and are the major source of type I collagen and the potent collagenase inhibitors tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) in the fibrotic liver. The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis.
Aims: To determine the effects of relaxin on activated HSC.
Methods: Following isolation, HSC were activated by culture on plastic and exposed to relaxin (1-100 ng/ml). Collagen deposition was determined by Sirius red dye binding and radiolabelled proline incorporation. Matrix metalloproteinase (MMP) and TIMP expression were assessed by zymography and northern analysis. Transforming growth factor beta 1 (TGF-beta 1) mRNA and protein levels were quantified by northern analysis and ELISA, respectively.
Results: Exposure of activated HSC to relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition. There was a parallel decrease in TIMP-1 and TIMP-2 secretion into the HSC conditioned media but no change in gelatinase expression was observed. Northern analysis demonstrated that primary HSC, continuously exposed to relaxin, had decreased TIMP-1 mRNA expression but unaltered type I collagen, collagenase (MMP-13), alpha smooth muscle actin, and TGF-beta 1 mRNA expression.
Conclusion: These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.
relaxin, hepatic stellate cell, hepatic fibrosis, type i collagen
0017-5749
577-583
Williams, E.J.
eff8aff3-c1af-4c16-89a6-bc9d4c7bd87e
Benyon, R.C.
11d7f1b7-3974-497e-9169-acd695de45ee
Trim, N.
482050d9-e709-4177-8221-4ecfdefdba64
Hadwin, R.
9118d266-5e5a-4500-bd98-8b26abb4fc43
Grove, B.H.
d688c283-a7f8-4f30-8865-49e883d3ac9f
Arthur, M.J.P.
645c7765-0205-4948-a357-6fe36f28b08a
Unemori, E.N.
422c1a55-4203-4d81-b888-9d2890e14225
Iredale, J.P.
5c8dbd67-954f-4a50-b084-af1d253277cb
Williams, E.J.
eff8aff3-c1af-4c16-89a6-bc9d4c7bd87e
Benyon, R.C.
11d7f1b7-3974-497e-9169-acd695de45ee
Trim, N.
482050d9-e709-4177-8221-4ecfdefdba64
Hadwin, R.
9118d266-5e5a-4500-bd98-8b26abb4fc43
Grove, B.H.
d688c283-a7f8-4f30-8865-49e883d3ac9f
Arthur, M.J.P.
645c7765-0205-4948-a357-6fe36f28b08a
Unemori, E.N.
422c1a55-4203-4d81-b888-9d2890e14225
Iredale, J.P.
5c8dbd67-954f-4a50-b084-af1d253277cb

Williams, E.J., Benyon, R.C., Trim, N., Hadwin, R., Grove, B.H., Arthur, M.J.P., Unemori, E.N. and Iredale, J.P. (2001) Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo. Gut, 49 (4), 577-583.

Record type: Article

Abstract

Background: Following liver injury, hepatic stellate cells (HSC) transform into myofibroblast-like cells (activation) and are the major source of type I collagen and the potent collagenase inhibitors tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) in the fibrotic liver. The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis.
Aims: To determine the effects of relaxin on activated HSC.
Methods: Following isolation, HSC were activated by culture on plastic and exposed to relaxin (1-100 ng/ml). Collagen deposition was determined by Sirius red dye binding and radiolabelled proline incorporation. Matrix metalloproteinase (MMP) and TIMP expression were assessed by zymography and northern analysis. Transforming growth factor beta 1 (TGF-beta 1) mRNA and protein levels were quantified by northern analysis and ELISA, respectively.
Results: Exposure of activated HSC to relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition. There was a parallel decrease in TIMP-1 and TIMP-2 secretion into the HSC conditioned media but no change in gelatinase expression was observed. Northern analysis demonstrated that primary HSC, continuously exposed to relaxin, had decreased TIMP-1 mRNA expression but unaltered type I collagen, collagenase (MMP-13), alpha smooth muscle actin, and TGF-beta 1 mRNA expression.
Conclusion: These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.

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More information

Published date: 2001
Keywords: relaxin, hepatic stellate cell, hepatic fibrosis, type i collagen

Identifiers

Local EPrints ID: 27488
URI: http://eprints.soton.ac.uk/id/eprint/27488
ISSN: 0017-5749
PURE UUID: d6614779-3e78-4c85-b3a0-b5157fd7e08d

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Date deposited: 28 Apr 2006
Last modified: 08 Jan 2022 18:54

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Contributors

Author: E.J. Williams
Author: R.C. Benyon
Author: N. Trim
Author: R. Hadwin
Author: B.H. Grove
Author: M.J.P. Arthur
Author: E.N. Unemori
Author: J.P. Iredale

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