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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-21
pubmed:abstractText
Plasma fibronectin (FN) has a broad range of biological functions involved in cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, reticuloendothelial system function, and ischemic injury. In this study, we examined the effects of FN on D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant liver failure in mice. Female Balb/c mice received intraperitoneal injection of 50 mug/kg of LPS and 400 mg/kg of GalN simultaneously. Thirty minutes before GalN/LPS administration, human plasma FN (FN group) or the same dose of human serum albumin (control group) was given intravenously. GalN/LPS induced a marked decrease in plasma FN, which was reversed by FN pretreatment. The survival rate of the FN group was markedly improved in a dose-dependent manner compared with that of the control group (survival rate 0%). FN prevented increases in the concentrations of serum enzymes and total bilirubin related to liver injury. FN pretreatment significantly suppressed tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 levels, and enhanced IL-10 levels in serum and liver tissue compared with the control group. Moreover, TUNEL staining, caspase 3 and 8 activities, and necrosis in the remnant liver were significantly decreased in the FN-treated rats compared with the controls. Furthermore, FN pretreatment inhibited the activation of nuclear factor (NF)-kappaB and increased the expression of Bcl-xL protein in liver tissue. These results suggest that FN protected against GalN/LPS-induced liver failure by a mechanism involving inhibition of NF-kappaB activation, which caused down-regulation of TNF-alpha and involved up-regulation of IL-10, and elevation of Bcl-xL induced a blockage of apoptotic signals, by which apoptosis of hepatocytes caused by GalN/LPS was suppressed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1073-2322
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
80-7
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Fibronectin prevents D-galactosamine/lipopolysaccharide-induced lethal hepatic failure in mice.
pubmed:affiliation
Department of Surgery, Kansai Medical University, Osaka 570-8507, Japan.
pubmed:publicationType
Journal Article