| Fibronectin is essential for survival but is dispensable for proliferation of hepatocytes in acute liver injury. | |
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MedLine Citation:
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PMID: 22318920 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Acute liver injury causes massive hepatocyte apoptosis and/or fatal liver damage. Fibronectin, an extracellular matrix glycoprotein, is prominently expressed during adult tissue repair. However, the extent of fibronectin dependence on the hepatocyte response to acute liver damage remains to be defined. As identification of hepatic survival factors is critical for successful therapeutic intervention in liver failure, this relationship has been investigated using a fibronectin-deficient mouse model of acute liver injury. Here we show that the lack of fibronectin induces significantly increased hepatocyte apoptosis, which is accompanied by significant downregulation of the anti-apoptotic protein Bcl-xL. Furthermore, fibronectin deficiency leads to a significantly elevated production of hepatocyte growth factor in hepatic stellate cells post injury, which in turn results in an earlier onset and acceleration of hepatocyte regeneration. Primary hepatocytes on fibronectin are protected from reactive oxygen species (ROS)-induced cellular damage, retaining expression of Bcl-xL, whereas those on type I collagen are not. This retained expression of Bcl-xL is inhibited by PI3-kinase inhibitor LY294002. Conclusion: We provide evidence that the fibronectin-mediated matrix survival signals for hepatocytes are transduced through the PI3-kinase-Bcl-xL signaling axis in response to injury. This work defines fibronectin as a novel anti-apoptotic factor for hepatocytes following acute liver injury but demonstrates that fibronectin is not essential for subsequent hepatocyte proliferation. (HEPATOLOGY 2012.). |
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Authors:
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Kei Moriya; Keiko Sakai; Michel H Yan; Takao Sakai |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-9 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Association for the Study of Liver Diseases. |
Affiliation:
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Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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