Publication: 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
Authors
Díaz-Gil, Juan J. ; García-Monzón, Carmelo ; Rúa, Carmen ; Martín Sanz, Paloma ; Cereceda, Rosa M. ; Machín, Celia ; Fernández Martínez, Amalia ; Miquilena-Colina, María E. ; García Cañero, Rafael
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Liver 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.
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