| MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-kappaB signaling. | |
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MedLine Citation:
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PMID: 20167875 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During liver regeneration, normally quiescent liver cells reenter the cell cycle, nonparenchymal and parenchymal cells divide, and proper liver architecture is restored. The gene expression programs regulating these transitions are not completely understood. MicroRNAs are a newly discovered class of small regulatory RNAs that silence messenger RNAs by binding to their 3'-untranslated regions (UTRs). A number of microRNAs, including miR-21, have been shown to be involved in regulation of cell proliferation. We performed partial hepatectomies on mice and allowed the liver to regenerate for 1, 6, 12, 24, and 48 h and 4 and 7 days. We compared the expression of miR-21 in the posthepatectomy liver to the prehepatectomy liver by Northern blot and found that miR-21 was upregulated during the early stages of liver regeneration. NF-kappaB signaling is also activated very early during liver regeneration. It has been previously reported that NF-kappaB upregulates the miR-21 precursor transcript. The predicted miR-21 target, Pellino (Peli1), is a ubiquitin ligase involved in activating NF-kappaB signaling. We observed an inverse correlation between miR-21 and Peli1 mRNA levels during liver regeneration. miR-21 overexpression in cultured cells inhibited a Peli1 3'-UTR luciferase reporter. Using NF-kappaB reporter assays, we determined that miR-21 overexpression inhibits NF-kappaB signaling. In conclusion, miR-21 expression was upregulated during early stages of liver regeneration. Targeting of Peli1 by miR-21 could potentially provide the basis for a negative feedback cycle regulating NF-kappaB signaling. |
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Authors:
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Rebecca T Marquez; Erik Wendlandt; Courtney Searcey Galle; Kathy Keck; Anton P McCaffrey |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-02-18 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 298 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-22 Completed Date: 2010-04-16 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G535-41 Citation Subset: IM |
Affiliation:
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University of Iowa School of Medicine, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3' Untranslated Regions
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genetics Animals Cell Line Gene Expression / drug effects, genetics Gene Expression Regulation / physiology* Genes, Reporter / genetics Humans Interleukin-6 / genetics Lipopolysaccharides / pharmacology Liver Regeneration / physiology* Mice Mice, Inbred C57BL MicroRNAs / genetics, metabolism* Models, Biological Mutation / genetics NF-kappa B / genetics, metabolism* Nuclear Proteins / genetics, metabolism* Signal Transduction / drug effects, physiology* Toll-Like Receptor 4 / genetics, metabolism Transfection Up-Regulation / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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T32AI007533/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3' Untranslated Regions; 0/Interleukin-6; 0/Lipopolysaccharides; 0/MIRN21 microRNA, mouse; 0/MicroRNAs; 0/NF-kappa B; 0/Nuclear Proteins; 0/Peli1 protein, mouse; 0/Toll-Like Receptor 4; 0/lipid-linked oligosaccharides |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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