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rdf:type |
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lifeskim:mentions |
umls-concept:C0010868,
umls-concept:C0016059,
umls-concept:C0026336,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0035820,
umls-concept:C0205263,
umls-concept:C0205314,
umls-concept:C0214743,
umls-concept:C0679622,
umls-concept:C2318511
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pubmed:issue |
7
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pubmed:dateCreated |
2008-9-19
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pubmed:abstractText |
Nonalcoholic steatohepatitis (NASH), the most common cause of chronic liver fibrosis, progresses to cirrhosis in up to 20% of patients. We report that hepatic stellate cells (HSC) in sinusoidal lesions of liver of patients with NASH express high levels of high-affinity IL-13R (IL-13Ralpha2), which is colocalized with smooth muscle actin, whereas fatty liver and normal liver specimens do not express IL-13Ralpha2. HSCs engineered to overexpress IL-13Ralpha2 respond to IL-13 and induce TGFB1 promoter activity and TGF-beta1 production. We also developed NASH in rats by feeding a choline-deficient l-amino acid diet. These rats developed liver fibrosis as assessed by H&E staining, Masson's trichrome and Sirius red staining, and hydroxyproline assays. Treatment of these rats with IL-13R-directed cytotoxin caused a substantial decline in fibrosis and liver enzymes without organ toxicity. These studies demonstrate that functional IL-13Ralpha2 are overexpressed in activated HSCs involved in NASH and that IL-13 cytotoxin ameliorates pathological features of NASH in rat liver, indicating a novel role of this cytotoxin in potential therapy.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
181
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4656-65
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pubmed:meshHeading |
pubmed-meshheading:18802068-Animals,
pubmed-meshheading:18802068-Cell Line,
pubmed-meshheading:18802068-Cell Line, Tumor,
pubmed-meshheading:18802068-Cells, Cultured,
pubmed-meshheading:18802068-Cytotoxins,
pubmed-meshheading:18802068-Disease Models, Animal,
pubmed-meshheading:18802068-Exotoxins,
pubmed-meshheading:18802068-Fatty Liver,
pubmed-meshheading:18802068-Gene Expression Regulation,
pubmed-meshheading:18802068-Hepatic Stellate Cells,
pubmed-meshheading:18802068-Humans,
pubmed-meshheading:18802068-Interleukin-13,
pubmed-meshheading:18802068-Interleukin-13 Receptor alpha2 Subunit,
pubmed-meshheading:18802068-Liver Cirrhosis,
pubmed-meshheading:18802068-Male,
pubmed-meshheading:18802068-RNA, Messenger,
pubmed-meshheading:18802068-Rats,
pubmed-meshheading:18802068-Rats, Inbred F344,
pubmed-meshheading:18802068-Receptors, Interleukin-13,
pubmed-meshheading:18802068-Recombinant Fusion Proteins,
pubmed-meshheading:18802068-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
Novel role of IL-13 in fibrosis induced by nonalcoholic steatohepatitis and its amelioration by IL-13R-directed cytotoxin in a rat model.
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pubmed:affiliation |
Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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pubmed:publicationType |
Journal Article
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