Autophagy protects the proximal tubule from degeneration and acute ischemic injury

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

Research output: Contribution to journalArticle

254 Citations (Scopus)

Abstract

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 autophagydeficient 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.

Original languageEnglish
Pages (from-to)902-913
Number of pages12
JournalJournal of the American Society of Nephrology
Volume22
Issue number5
DOIs
Publication statusPublished - 2011 May 1

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Kimura, T., Takabatake, Y., Takahashi, A., Kaimori, J. Y., Matsui, I., Namba, T., Kitamura, H., Niimura, F., Matsusaka, T., Soga, T., Rakugi, H., & Isaka, Y. (2011). Autophagy protects the proximal tubule from degeneration and acute ischemic injury. Journal of the American Society of Nephrology, 22(5), 902-913. https://doi.org/10.1681/ASN.2010070705