Document Detail


Autophagy fuels tissue fibrogenesis.
MedLine Citation:
PMID:  22617442     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Virginia Hernández-Gea; Scott L Friedman
Publication Detail:
Type:  Journal Article     Date:  2012-05-01
Journal Detail:
Title:  Autophagy     Volume:  8     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2012-11-13     Revised Date:  2014-04-18    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  849-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy*
Hepatic Stellate Cells / pathology
Humans
Kidney / pathology
Lipids / chemistry
Liver / pathology*
Liver Cirrhosis / pathology*
Lung / pathology
Mice
Models, Biological
Grant Support
ID/Acronym/Agency:
R01 AA020709/AA/NIAAA NIH HHS; R01 DK056621/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Lipids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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