Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis

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dc.contributor.authorIredale J.P.
dc.contributor.authorBenyon R.C.
dc.contributor.authorArthur M.J.P.
dc.contributor.authorFerris W.F.
dc.contributor.authorAlcolado R.
dc.contributor.authorWinwood P.J.
dc.contributor.authorClark N.
dc.contributor.authorMurphy G.
dc.date.accessioned2011-05-15T16:16:31Z
dc.date.available2011-05-15T16:16:31Z
dc.date.issued1996
dc.description.abstractLiver fibrosis results from a relative imbalance between synthesis and degradation of matrix proteins. We have previously described release of the potent collagen-use inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP- 1), by culture-activated human hepatic stellate cells (HSCs). In this study, we have investigated the relative expression of TIMP-1 and interstitial collagenase in culture-activated rat HSCs and rat models of liver injury and fibrosis. The complementary DNA (cDNA) for rat TIMP-1 was obtained by homology polymerase chain reaction (PCR) and sequenced. By Northern analysis using this probe, TIMP-1 messenger RNA (mRNA) expression was up-regulated with HSC activation by culture on plastic as defined by cellular expression of procollagen-1. Interstitial collagenase mRNA was expressed in early culture (<4 days) but became undetectable in more activated cells (7-21 days). By activity assay of serum-free cell-conditioned media, TIMP-1 was found to be released in increasing concentrations with duration of culture on plastic. Expression of TIMP-1, interstitial collagenase, and procollagen-1 mRNAs were studied in rat models of biliary and parenchymal injury (bile duct ligation and CCl4 administration) by ribonuclease protection assay. TIMP-1 mRNA expression was increased at 6, 24 hours, and 3 days after bile duct ligation and was also shown to rise in acute CCl4 liver injury and remain elevated as the liver became fibrotic. TIMP-1 expression preceded procollagen-1 expression in both models. In contrast, interstitial collagenase mRNA levels remained similar to control values throughout both models of liver injury. Total cellular RNA from hepatocytes, HSCs, and Kupffer cells freshly isolated from livers after acute CCl4 injury was subjected to Northern analysis. TIMP-1 transcripts were observed in nonparenchymal cells only. We suggest that increased expression of TIMP-1 relative to interstitial collagenase by HSCs may promote progression of liver fibrosis in these rat models by preventing degradation of secreted collagens.
dc.description.versionArticle
dc.identifier.citationHepatology
dc.identifier.citation24
dc.identifier.citation1
dc.identifier.issn02709139
dc.identifier.other10.1053/jhep.1996.v24.pm0008707259
dc.identifier.urihttp://hdl.handle.net/10019.1/13821
dc.subjectcarbon tetrachloride
dc.subjectcollagen type 1
dc.subjectcollagenase
dc.subjectcomplementary dna
dc.subjectmessenger rna
dc.subjectprocollagen
dc.subjecttissue inhibitor of metalloproteinase
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectarticle
dc.subjectbile duct ligation
dc.subjectcontrolled study
dc.subjectgene expression
dc.subjectliver cell
dc.subjectliver fibrosis
dc.subjectliver injury
dc.subjectmale
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectrat
dc.subjectstellate cell
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectBile Ducts
dc.subjectBlotting, Northern
dc.subjectBlotting, Western
dc.subjectCattle
dc.subjectCells, Cultured
dc.subjectCloning, Molecular
dc.subjectCollagenases
dc.subjectGlycoproteins
dc.subjectHumans
dc.subjectLiver
dc.subjectLiver Cirrhosis, Experimental
dc.subjectMatrix Metalloproteinase 1
dc.subjectMice
dc.subjectMolecular Sequence Data
dc.subjectPolymerase Chain Reaction
dc.subjectRabbits
dc.subjectRats
dc.subjectRNA, Messenger
dc.subjectSequence Homology, Amino Acid
dc.subjectTissue Inhibitor of Metalloproteinases
dc.subjectTranscription, Genetic
dc.titleTissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis
dc.typeArticle
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