Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-11-20
pubmed:abstractText
Signaling through tumor necrosis factor receptor type 1 (TNFR-1) using a pathway that involves nuclear factor kappaB (NF-kappaB), interleukin-6 (IL-6), and STAT3 is required for the initiation of liver regeneration. We have proposed that TNF primes hepatocytes to respond to the mitogenic effect of growth factors, but so far, there has been no experimental demonstration that TNF enhances growth factor responses of hepatocytes. To test this hypothesis, we infused hepatocyte growth factor (HGF) and transforming growth factor (TGF-) (40 microgram/24 h) directly into the portal vein of rats for 24 hours using osmotic pumps and determined whether TNF injection (5 microgram per rat) would significantly increase hepatocyte DNA labeling in these animals. All rats received 5-bromo-2'-deoxyuridine (BrdU) by intraperitoneal delivery during a 48-hour period (i.e., BrdU infusion continued for 24 hours after the end of growth factor administration). BrdU labeling in the liver was measured by both immunohistochemistry and flow cytometry, and the results obtained by these methods showed excellent concordance. The results demonstrate that TNF transiently activates NF-kappaB and STAT3 and increases the proliferative response of hepatocytes to HGF or TGF- by fourfold. Priming effects on hepatocyte DNA replication were also obtained with injection of lipopolysaccharide (LPS) and gadolinium chloride (GdCl3), agents that release TNF in the liver. Similarly to TNF, GdCl3 injection caused the activation of NF-kappaB and STAT3, reaching a maximum 8 to 12 hours after the injection. The results show that TNF acts as a primer to sensitize hepatocytes to the proliferative effects of growth factors and offers a mechanism to explain the initiation and progression phases of liver regeneration after partial hepatectomy (PH).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Gadolinium, http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor, http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/gadolinium chloride
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1226-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9794905-Animals, pubmed-meshheading:9794905-Cell Division, pubmed-meshheading:9794905-DNA Replication, pubmed-meshheading:9794905-DNA-Binding Proteins, pubmed-meshheading:9794905-Flow Cytometry, pubmed-meshheading:9794905-Gadolinium, pubmed-meshheading:9794905-Hepatocyte Growth Factor, pubmed-meshheading:9794905-Interleukin-6, pubmed-meshheading:9794905-Kinetics, pubmed-meshheading:9794905-Lipopolysaccharides, pubmed-meshheading:9794905-Liver, pubmed-meshheading:9794905-Male, pubmed-meshheading:9794905-NF-kappa B, pubmed-meshheading:9794905-Rats, pubmed-meshheading:9794905-Rats, Sprague-Dawley, pubmed-meshheading:9794905-Receptors, Tumor Necrosis Factor, pubmed-meshheading:9794905-STAT3 Transcription Factor, pubmed-meshheading:9794905-Signal Transduction, pubmed-meshheading:9794905-Trans-Activators, pubmed-meshheading:9794905-Transforming Growth Factor alpha, pubmed-meshheading:9794905-Tumor Necrosis Factor-alpha
pubmed:year
1998
pubmed:articleTitle
Tumor necrosis factor primes hepatocytes for DNA replication in the rat.
pubmed:affiliation
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't