Document Detail


Autophagy protects the proximal tubule from degeneration and acute ischemic injury.
MedLine Citation:
PMID:  21493778     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autophagy is a bulk protein degradation system that likely plays an important role in normal proximal tubule function and recovery from acute ischemic kidney injury. Using conditional Atg5 gene deletion to eliminate autophagy in the proximal tubule, we determined whether autophagy prevents accumulation of damaged proteins and organelles with aging and ischemic renal injury. Autophagy-deficient cells accumulated deformed mitochondria and cytoplasmic inclusions, leading to cellular hypertrophy and eventual degeneration not observed in wildtype controls. In autophagy-deficient mice, I/R injury increased proximal tubule cell apoptosis with accumulation of p62 and ubiquitin positive cytoplasmic inclusions. Compared with control animals, autophagy-deficient mice exhibited significantly greater elevations in serum urea nitrogen and creatinine. These data suggest that autophagy maintains proximal tubule cell homeostasis and protects against ischemic injury. Enhancing autophagy may provide a novel therapeutic approach to minimize acute kidney injury and slow CKD progression.
Authors:
Tomonori Kimura; Yoshitsugu Takabatake; Atsushi Takahashi; Jun-ya Kaimori; Isao Matsui; Tomoko Namba; Harumi Kitamura; Fumio Niimura; Taiji Matsusaka; Tomoyoshi Soga; Hiromi Rakugi; Yoshitaka Isaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-14
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  22     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-07-01     Revised Date:  2012-05-01    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  902-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 by the American Society of Nephrology
Affiliation:
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acute Kidney Injury / prevention & control*
Animals
Autophagy*
Hypertrophy
Kidney / blood supply*,  pathology
Kidney Tubules, Proximal / pathology*
Male
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins / physiology
Reperfusion Injury / prevention & control*
Chemical
Reg. No./Substance:
0/Atg5 protein, mouse; 0/Microtubule-Associated Proteins

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


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