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Regulation of the synthesis of tissue inhibitors of metalloproteinase-1 and -2 by hepatic and pancreatic stellate cells

Regulation of the synthesis of tissue inhibitors of metalloproteinase-1 and -2 by hepatic and pancreatic stellate cells
Regulation of the synthesis of tissue inhibitors of metalloproteinase-1 and -2 by hepatic and pancreatic stellate cells
Hepatic stellate cells (HSC) play a central role in fibrosis development by production of extracellular matrix and also by secretion of matrix metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPs) including TIMP-2 and MMP-2. TIMP-2 has been shown to interact with Gelatinase A in conjunction with MT1-MMP (MMP-14). TIMP-2 has been traditionally considered to be constitutively expressed. There is some evidence that TIMP-2 expression is slightly enhanced in fibrotic disease and activation in tissue culture. Little is known in terms of TIMP-2 expression in the recently described pancreatic stellate cells (PSC). HSC were cultured on plastic having been isolated from rat and human liver resections. After culture on plastic northern analysis was performed for TIMP-2 mRNA expression. TIMP-2 promoter activity was examined in rat pancreatic stellate cells (PSC) and rat hepatic stellate cells. Early work led to subcloning the promoter into a different vector though subsequent promoter studies were unsuccessful. In vivo work in immunohistochemistry studies suggest there is increased TIMP-2 expression in evaluation of rat pancreas and liver in addition to human liver and pancreas specimens. By ribonuclease protection assay TIMP-2 was noted to be upregulated in human fibrotic liver compared to normal human liver tissue. In conclusion there is some evidence that TIMP-2 regulation may be altered in fibrotic liver states as well as in pancreatic inflammatory disease.
McCrudden, Peter Raymond
44ea907f-72fd-4970-bdc7-7556b3a13c61
McCrudden, Peter Raymond
44ea907f-72fd-4970-bdc7-7556b3a13c61
Iredale, John P.
607673ce-77b2-4418-b317-2aa778110ee2
Benyon, Christopher
f82e4f7f-c1fd-422d-a36d-ad04b59e855d

(2010) Regulation of the synthesis of tissue inhibitors of metalloproteinase-1 and -2 by hepatic and pancreatic stellate cells. University of Southampton, Faculty of Medicine, Doctoral Thesis, 305pp.

Record type: Thesis (Doctoral)

Abstract

Hepatic stellate cells (HSC) play a central role in fibrosis development by production of extracellular matrix and also by secretion of matrix metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPs) including TIMP-2 and MMP-2. TIMP-2 has been shown to interact with Gelatinase A in conjunction with MT1-MMP (MMP-14). TIMP-2 has been traditionally considered to be constitutively expressed. There is some evidence that TIMP-2 expression is slightly enhanced in fibrotic disease and activation in tissue culture. Little is known in terms of TIMP-2 expression in the recently described pancreatic stellate cells (PSC). HSC were cultured on plastic having been isolated from rat and human liver resections. After culture on plastic northern analysis was performed for TIMP-2 mRNA expression. TIMP-2 promoter activity was examined in rat pancreatic stellate cells (PSC) and rat hepatic stellate cells. Early work led to subcloning the promoter into a different vector though subsequent promoter studies were unsuccessful. In vivo work in immunohistochemistry studies suggest there is increased TIMP-2 expression in evaluation of rat pancreas and liver in addition to human liver and pancreas specimens. By ribonuclease protection assay TIMP-2 was noted to be upregulated in human fibrotic liver compared to normal human liver tissue. In conclusion there is some evidence that TIMP-2 regulation may be altered in fibrotic liver states as well as in pancreatic inflammatory disease.

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Published date: June 2010
Organisations: University of Southampton, Faculty of Medicine

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Local EPrints ID: 372931
URI: http://eprints.soton.ac.uk/id/eprint/372931
PURE UUID: c35a6926-f445-4b12-a1e0-cd09b6082cab

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Date deposited: 19 Jan 2015 14:29
Last modified: 17 Jul 2017 21:37

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Contributors

Author: Peter Raymond McCrudden
Thesis advisor: John P. Iredale
Thesis advisor: Christopher Benyon

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