title: Differential expression of matrix-metalloproteinase-1 and -2 genes in normal and fibrotic human liver.
abstract: Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We investigated levels and cellular sites of gene expression of two major collagen-degrading enzymes, matrix-metalloproteinase (MMP)-1 (fibroblast type-interstitial collagenase) and MMP-2 (72-kd gelatinase, type IV collagenase) in five normal and 18 fibrotic human livers as well as in cultured human hepatic fat-storing cells by Northern blot analysis and in situ hybridization. Fat-storing cells expressed both MMP-1 and MMP-2 RNA in vitro. In vivo, MMP-1 was undetectable in mesenchymal and parenchymal cells of all liver specimens, whereas MMP-2 transcripts were expressed in all livers by vimentin-positive, CD68-negative mesenchymal cells. Mesenchymal cells of all fibrotic livers displayed high transcript levels of transforming growth factor-beta 1, which is known to modulate MMP expression. Along with de novo fibrogenesis and possibly influenced by transforming growth factor-beta 1, expression of MMP-2 in the absence of MMP-1 expression may be responsible for the quantitative and qualitative changes of extracellular matrix observed in chronic liver disease.
authors.affiliation: Gastroenterology Unit, University of Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Milani
authors.forename: H
authors.initials: H
authors.lastname: Herbst
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.forename: C
authors.initials: C
authors.lastname: Grappone
authors.forename: G
authors.initials: G
authors.lastname: Pellegrini
authors.forename: M
authors.initials: M
authors.lastname: Pinzani
authors.forename: A
authors.initials: A
authors.lastname: Casini
authors.forename: A
authors.initials: A
authors.lastname: Calabró
authors.forename: G
authors.initials: G
authors.lastname: Ciancio
authors.forename: F
authors.initials: F
authors.lastname: Stefanini
mesh_terms: D001345:Autoradiography; D015152:Blotting, Northern; D002478:Cells, Cultured; D017364:Collagenases / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D018093:Gelatinases / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry* / Q000166:cytology / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1