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Publication : Autophagy protects the proximal tubule from degeneration and acute ischemic injury.

First Author  Kimura T Year  2011
Journal  J Am Soc Nephrol Volume  22
Issue  5 Pages  902-13
PubMed ID  21493778 Mgi Jnum  J:179961
Mgi Id  MGI:5304935 Doi  10.1681/ASN.2010070705
Citation  Kimura T, et al. (2011) Autophagy protects the proximal tubule from degeneration and acute ischemic injury. J Am Soc Nephrol 22(5):902-13
abstractText  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.
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