| E-box-binding repressor is down-regulated in hepatic stellate cells during up-regulation of mannose 6-phosphate/insulin-like growth factor-II receptor expression in early hepatic fibrogenesis. | |
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MedLine Citation:
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PMID: 9632637 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hepatic stellate cells become activated during the early stages of hepatic injury associated with fibrogenesis. The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGFIIR) plays an important role in early fibrogenesis by participating in the activation of latent transforming growth factor-beta, a potent inducer of the matrix proteins in activated stellate cells that define the fibrotic phenotype. In this study we examined hepatic stellate cell regulation of M6P/IGFIIR expression and found that M6P/IGFIIR mRNA transcript levels increased in stellate cells from rats exposed to carbon tetrachloride (CCl4), a potent fibrogenic stimulant. Two E-boxes residing in the proximal promoter of M6P/IGFIIR were found to each bind a novel 75-kDa transcription factor (P75) in quiescent stellate cells of normal livers. This E-box binding was down-regulated as an early response in stellate cells exposed to CCl4, coinciding with increased M6P/IGFIIR transcript levels. Mutagenized E-boxes in M6P/IGFIIR promoter-chloramphenicol acetyltransferase (CAT) reporter constructs produced a substantial increase in reporter expression when compared with the corresponding native promoter-CAT construct when transfected in culture-activated stellate cells, suggesting P75's role as a repressor. The results indicate P75's participation in the regulation of M6P/IGFIIR transcription in hepatic stellate cells during fibrogenesis. |
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Authors:
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J A Weiner; A Chen; B H Davis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 273 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1998 Jun |
Date Detail:
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Created Date: 1998-08-03 Completed Date: 1998-08-03 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 15913-9 Citation Subset: IM |
Affiliation:
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Gastroenterology Section, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois 60637, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbon Tetrachloride Poisoning / metabolism, pathology DNA / metabolism Down-Regulation Liver / cytology*, metabolism Liver Cirrhosis, Experimental / chemically induced, metabolism*, pathology Male Molecular Weight Mutagenesis, Site-Directed Promoter Regions, Genetic / genetics RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Receptor, IGF Type 2 / biosynthesis* Repressor Proteins / biosynthesis*, metabolism Transfection Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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DK 42086/DK/NIDDK NIH HHS; DK02022/DK/NIDDK NIH HHS; DK40223/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Receptor, IGF Type 2; 0/Repressor Proteins; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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