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The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats

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dc.contributor.authorDíaz-Gil, Juan J.es
dc.contributor.authorGarcía-Monzón, Carmeloes
dc.contributor.authorRúa, Carmen
dc.contributor.authorMartín Sanz, Paloma
dc.contributor.authorCereceda, Rosa M.
dc.contributor.authorMachín, Celia
dc.contributor.authorFernández Martínez, Amalia
dc.contributor.authorMiquilena-Colina, María E.
dc.contributor.authorGarcía Cañero, Rafael
dc.date.accessioned2013-01-22T10:01:05Z
dc.date.available2013-01-22T10:01:05Z
dc.date.issued2008
dc.description.abstractLiver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile ductligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 μg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-ß1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-ß1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-ß1 in fibrotic rats.es
dc.formatapplication/pdfes
dc.format.extent9es
dc.identifier.issn0213-3911es
dc.identifier.urihttp://hdl.handle.net/10201/29802
dc.languageenges
dc.publisherMurcia : F. Hernándezes
dc.relation.ispartofHistology and histopathologyes
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectCirrhosises
dc.subjectFibrosises
dc.subject.other577 - Bioquímica. Biología molecular. Biofísicaes
dc.titleThe anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated ratses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.23, nº5 (2008)