Expression of matrix metalloproteinase-2 and -14 persists during early resolution of experimental liver fibrosis and might contribute to fibrolysis
Expression of matrix metalloproteinase-2 and -14 persists during early resolution of experimental liver fibrosis and might contribute to fibrolysis
Abstract: Background/Aims: Resolution of liver fibrosis is possible but the identity of the matrix metalloproteinases (MMPs) which degrade the accumulated collagens is uncertain. We examined MMP-2 and MMP-14 expression in established and resolving fibrosis to assess their role in resolution of liver fibrosis.
Methods: MMP and tissue inhibitor of metalloproteinase (TIMP)-2 expression in liver extracts was examined by ribonuclease protection assay, Western blotting and gelatin zymography. MMP activity was examined by 14C gelatin degradation.
Results: In human cirrhotic liver, MMP-14 mRNA was increased to 230–330% of normal liver expression. Both 63 kDa proenzyme and 60 kDa activated form were present. Cirrhotic livers had 270–320% of normal liver expression of MMP-2 protein with 20–25% being the 62 Da activated form. Protein and mRNA for MMP-2 and MMP-14 progressively increased during 8 weeks of CCl4 treatment in rats. Between 3 and 7 days of resolution from CCl4 liver fibrosis, MMP-2 and MMP-14 persisted at elevated levels. Gelatinolytic activity in liver homogenates peaked at 7 days of recovery, being 140% above that in livers at peak fibrosis.
Conclusions: Increased expression and activation of MMP-2 and -14 occurs even under conditions of elevated TIMPs during liver fibrogenesis. During liver fibrosis resolution, as TIMP expression decays, the persistence of MMP-2 and MMP-14 may permit collagen degradation.
collagenase, hepatic stellate cell, liver fibrosis, matrix metalloproteinase, tissue inhibitor of metalloproteinase
492-501
Zhou, Xiaoying
52423958-8092-4391-9e96-e7422c12e1b9
Hovell, Christopher J.
057ab899-856d-4e6b-9bab-dc0b5ea808f1
Pawley, Susannah
94c25db1-bd13-48b0-9e13-66d5187fb4e2
Hutchings, Matthew I.
a4a6c75c-b14a-4131-bcbc-7d1ffdd29011
Arthur, Michael J.
0f430e69-59fb-401a-8aa5-343998f47887
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2
Benyon, R. Christopher
6efa9278-56e6-47ec-9854-78afd98dd4c9
October 2004
Zhou, Xiaoying
52423958-8092-4391-9e96-e7422c12e1b9
Hovell, Christopher J.
057ab899-856d-4e6b-9bab-dc0b5ea808f1
Pawley, Susannah
94c25db1-bd13-48b0-9e13-66d5187fb4e2
Hutchings, Matthew I.
a4a6c75c-b14a-4131-bcbc-7d1ffdd29011
Arthur, Michael J.
0f430e69-59fb-401a-8aa5-343998f47887
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2
Benyon, R. Christopher
6efa9278-56e6-47ec-9854-78afd98dd4c9
Zhou, Xiaoying, Hovell, Christopher J., Pawley, Susannah, Hutchings, Matthew I., Arthur, Michael J., Iredale, John P. and Benyon, R. Christopher
(2004)
Expression of matrix metalloproteinase-2 and -14 persists during early resolution of experimental liver fibrosis and might contribute to fibrolysis.
Liver International, 24 (5), .
(doi:10.1111/j.1478-3231.2004.0946.x).
Abstract
Abstract: Background/Aims: Resolution of liver fibrosis is possible but the identity of the matrix metalloproteinases (MMPs) which degrade the accumulated collagens is uncertain. We examined MMP-2 and MMP-14 expression in established and resolving fibrosis to assess their role in resolution of liver fibrosis.
Methods: MMP and tissue inhibitor of metalloproteinase (TIMP)-2 expression in liver extracts was examined by ribonuclease protection assay, Western blotting and gelatin zymography. MMP activity was examined by 14C gelatin degradation.
Results: In human cirrhotic liver, MMP-14 mRNA was increased to 230–330% of normal liver expression. Both 63 kDa proenzyme and 60 kDa activated form were present. Cirrhotic livers had 270–320% of normal liver expression of MMP-2 protein with 20–25% being the 62 Da activated form. Protein and mRNA for MMP-2 and MMP-14 progressively increased during 8 weeks of CCl4 treatment in rats. Between 3 and 7 days of resolution from CCl4 liver fibrosis, MMP-2 and MMP-14 persisted at elevated levels. Gelatinolytic activity in liver homogenates peaked at 7 days of recovery, being 140% above that in livers at peak fibrosis.
Conclusions: Increased expression and activation of MMP-2 and -14 occurs even under conditions of elevated TIMPs during liver fibrogenesis. During liver fibrosis resolution, as TIMP expression decays, the persistence of MMP-2 and MMP-14 may permit collagen degradation.
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Submitted date: 16 December 2003
Published date: October 2004
Additional Information:
Basic study
Keywords:
collagenase, hepatic stellate cell, liver fibrosis, matrix metalloproteinase, tissue inhibitor of metalloproteinase
Identifiers
Local EPrints ID: 27509
URI: http://eprints.soton.ac.uk/id/eprint/27509
ISSN: 1478-3223
PURE UUID: 19d63b20-33fa-4aaf-ae9e-5c7806ad9007
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Date deposited: 27 Apr 2006
Last modified: 15 Mar 2024 07:19
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Contributors
Author:
Xiaoying Zhou
Author:
Christopher J. Hovell
Author:
Susannah Pawley
Author:
Matthew I. Hutchings
Author:
Michael J. Arthur
Author:
John P. Iredale
Author:
R. Christopher Benyon
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