title: Expression of matrix metalloproteinase-2 and -9 and of tissue inhibitor of matrix metalloproteinase-1 in liver regeneration from oval cells in rat.
abstract: Oval cells participate in liver regeneration when hepatocyte replication is impaired. These precursor cells proliferate in periportal regions and organize in ductules. They are surrounded by a basement membrane, the degradation of which by matrix metalloproteinases (MMP) might trigger their terminal differentiation into hepatocytes. We studied the expression of MMP-2 and MMP-9 and that of one of their tissue inhibitors (TIMP-1) in a model of hepatic regeneration from precursor cells. Regeneration was induced by treating rats with 2-acetylaminofluorene followed by partial hepatectomy. MMP-2 and MMP-9 hepatic expression paralleled oval cell number with a peak at day 9-14 after hepatectomy. They were mainly detected in oval cells. TIMP-1 mRNA and oncostatin M receptor mRNA, a major regulator of TIMP-1 synthesis, markedly increased from day 1 after surgery until day 9 and then declined; they were mainly detected in interlobular bile duct cells and oval cells until day 14. In agreement with the in vivo data, the WB-F344 liver precursor cell line expressed MMP-2 and MMP-9, as well as TIMP-1 and oncostatin M receptor. These data suggest that (a) early increased TIMP-1 synthesis by biliary and oval cells favors basement membrane deposition around proliferating ductular structures through MMP inhibition, (b) delayed increased MMP expression, concomitant to decreased TIMP-1 synthesis, leads to basement membrane degradation, preceding oval cell differentiation, (c) the oncostatin M pathway might play a major role in increased TIMP-1 synthesis.
authors.affiliation: INSERM U841, Université Paris 12, AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Département de Pathologie, Créteil, F-94000 France.
authors.forename: T
authors.initials: T
authors.lastname: Pham Van
authors.forename: D
authors.initials: D
authors.lastname: Couchie
authors.forename: N
authors.initials: N
authors.lastname: Martin-Garcia
authors.forename: Y
authors.initials: Y
authors.lastname: Laperche
authors.forename: E S
authors.initials: ES
authors.lastname: Zafrani
authors.forename: P
authors.initials: P
authors.lastname: Mavier
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000201:enzymology; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology* / Q000201:enzymology*; D008115:Liver Regeneration / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D053677:Receptors, Oncostatin M / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053677:Receptors, Oncostatin M; D019715:Tissue Inhibitor of Metalloproteinase-1; D053683:Oncostatin M; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9