| Autophagy fuels tissue fibrogenesis. | |
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MedLine Citation:
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PMID: 22617442 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of hepatic stellate cells (HSC), a resident pericytic cell in liver, into a proliferative and fibrogenic cell type, is the principal event underlying hepatic fibrosis following injury. Release of lipid droplets (LD) containing retinyl esters and triglyceride is a defining feature of HSC activation, yet the basis for this release has remained mysterious. Here we offer a surprising discovery that autophagy is the missing link underlying LD release, by stimulating metabolism of their contents to provide the energy vital to fuel HSC activation. By specifically inhibiting the autophagic pathway in activated HSC, LD release is impaired and cellular ATP levels are decreased. Moreover, animals with HSC-specific deletion of Atg7 display attenuated activation following liver injury, leading to reduced fibrosis in vivo. We further demonstrate that fibrogenic cells from other organs, including kidney and lung, also rely on autophagy as a core pathway driving the scarring response. Our results provide a novel framework for understanding pathways underlying fibrogenic cell responses to tissue injury. |
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Authors:
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Virginia Hernández-Gea; Scott L Friedman |
Publication Detail:
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Type: Journal Article Date: 2012-05-01 |
Journal Detail:
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Title: Autophagy Volume: 8 ISSN: 1554-8635 ISO Abbreviation: Autophagy Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-08-27 Completed Date: 2012-11-13 Revised Date: 2013-01-10 |
Medline Journal Info:
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Nlm Unique ID: 101265188 Medline TA: Autophagy Country: United States |
Other Details:
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Languages: eng Pagination: 849-50 Citation Subset: IM |
Affiliation:
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Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autophagy* Hepatic Stellate Cells / pathology Humans Kidney / pathology Lipids / chemistry Liver / pathology* Liver Cirrhosis / pathology* Lung / pathology Mice Models, Biological |
| Chemical | |
Reg. No./Substance:
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0/Lipids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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