| Early growth response (Egr)-1 is required for timely cell cycle entry and progression in hepatocytes after acute carbon tetrachloride exposure in mice. | |
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MedLine Citation:
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PMID: 21415413 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background and Aims: Cell cycle induction in hepatocytes protects from prolonged tissue damage after toxic liver injury. Egr-1-/- mice exhibit increased liver injury after carbon tetrachloride (CCl(4)) exposure and reduced TNFα production. Since TNFα is required for prompt cell cycle induction after liver injury, here, we tested the hypothesis that Egr-1 is required for timely hepatocyte entry into the cell cycle after CCl(4)-induced liver injury. Methods: Acute liver injury was induced by a single injection of CCl(4). Assays were employed to assess indices of the cell cycle in liver after CCl(4) exposure. Results: Bromodeoxyuridine incorporation peaked in wild-type mice at 48h after CCl(4) but was reduced by 80% in egr-1-/- mice. Proliferating cell nuclear antigen immunohistochemistry revealed blocks in cell cycle entry and progression to DNA synthesis in Egr-1-deficient mice 48h after CCl(4) exposure. Cyclin D, important for G0/G1 progression, was reduced at baseline and 36h after CCl(4). Cyclin E1, required for G1/S-phase transition, was reduced in egr-1-/- mice 24 and 48h after CCl(4) exposure and was associated with reduced phosphorylation of the retinoblastoma protein. DNA synthesis in egr-1-/- mice was delayed, rather than blocked, since indices of cell cycle progression were restored 72h after CCl(4) exposure. Conclusions: Egr-1 was required for prompt cell cycle entry (G0 to G1) and G1/S-phase transition after toxic liver injury. These data support the hypothesis that Egr-1 provides hepatoprotection in the CCl(4)-injured liver due, in part, to timely cell cycle induction and progression. |
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Authors:
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Michele Teresa Pritchard; Robert N Malinak; Laura E Nagy |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-17 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: - ISSN: 1522-1547 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Cleveland Clinic. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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