Source:http://linkedlifedata.com/resource/pubmed/id/17952094
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2007-11-16
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| pubmed:abstractText |
Progenitors regenerate fatty livers but the mechanisms involved are uncertain. The Hedgehog pathway regulates mesendodermal progenitors and modulates mesenchymal-epithelial interactions during tissue remodeling. To determine if Hedgehog signaling increases in liver progenitors during fatty liver injury, we compared expression of Hedgehog ligands and target genes across a spectrum of injury. Leptin-deficient ob/ob mice with fatty livers and their healthy lean littermates were studied before and after exposure to the hepatotoxin, ethionine. At baseline, ob/ob mice had greater liver damage than controls. Ethionine induced liver injury in both ob/ob and lean mice, with greater injury occurring in ob/ob mice. After ethionine, the ob/ob mice developed liver atrophy and fibrosis. Liver injury increased hepatic accumulation of progenitors, including ductular cells that produced and responded to Hedgehog ligands. A dose-response relationship was demonstrated between liver injury and expansion of Hedgehog-responsive progenitors. In severely damaged, atrophic livers, nuclei in mature-appearing hepatocytes accumulated the Hedgehog-regulated mesenchymal transcription factor, Gli2 and lost expression of the liver epithelial transcription factor, hepatocyte nuclear factor 6 (HNF-6). Hepatic levels of collagen mRNA and pericellular collagen fibrils increased concomitantly. Hence, fatty liver injury increases Hedgehog activity in liver progenitors, and this might promote epithelial-mesenchymal transitions that result in liver fibrosis.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ethionine,
http://linkedlifedata.com/resource/pubmed/chemical/Gli3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hedgehog Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Leptin,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Onecut1 protein, mouse
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
1530-0307
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
87
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1227-39
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17952094-Animals,
pubmed-meshheading:17952094-Drug-Induced Liver Injury,
pubmed-meshheading:17952094-Ethionine,
pubmed-meshheading:17952094-Fatty Liver,
pubmed-meshheading:17952094-Hedgehog Proteins,
pubmed-meshheading:17952094-Hepatocyte Nuclear Factor 6,
pubmed-meshheading:17952094-Hepatocytes,
pubmed-meshheading:17952094-Kruppel-Like Transcription Factors,
pubmed-meshheading:17952094-Leptin,
pubmed-meshheading:17952094-Ligands,
pubmed-meshheading:17952094-Liver Cirrhosis, Experimental,
pubmed-meshheading:17952094-Male,
pubmed-meshheading:17952094-Mesenchymal Stem Cells,
pubmed-meshheading:17952094-Mice,
pubmed-meshheading:17952094-Mice, Inbred C57BL,
pubmed-meshheading:17952094-Mice, Obese,
pubmed-meshheading:17952094-Nerve Tissue Proteins,
pubmed-meshheading:17952094-Signal Transduction
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| pubmed:year |
2007
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| pubmed:articleTitle |
Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice.
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| pubmed:affiliation |
Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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