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

228 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

Fingerprint

Autophagy
Wounds and Injuries
Inclusion Bodies
Acute Kidney Injury
Recovery of Function
Gene Deletion
Ubiquitin
Organelles
Hypertrophy
Proteolysis
Urea
Creatinine
Mitochondria
Homeostasis
Nitrogen
Apoptosis
Kidney
Serum
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Kimura, T., Takabatake, Y., Takahashi, A., Kaimori, J. Y., Matsui, I., Namba, T., ... 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

Autophagy protects the proximal tubule from degeneration and acute ischemic injury. / Kimura, Tomonori; Takabatake, Yoshitsugu; Takahashi, Atsushi; Kaimori, Jun Ya; Matsui, Isao; Namba, Tomoko; Kitamura, Harumi; Niimura, Fumio; Matsusaka, Taiji; Soga, Tomoyoshi; Rakugi, Hiromi; Isaka, Yoshitaka.

In: Journal of the American Society of Nephrology, Vol. 22, No. 5, 05.2011, p. 902-913.

Research output: Contribution to journalArticle

Kimura, T, Takabatake, Y, Takahashi, A, Kaimori, JY, 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, vol. 22, no. 5, pp. 902-913. https://doi.org/10.1681/ASN.2010070705
Kimura, Tomonori ; Takabatake, Yoshitsugu ; Takahashi, Atsushi ; Kaimori, Jun Ya ; Matsui, Isao ; Namba, Tomoko ; Kitamura, Harumi ; Niimura, Fumio ; Matsusaka, Taiji ; Soga, Tomoyoshi ; Rakugi, Hiromi ; Isaka, Yoshitaka. / Autophagy protects the proximal tubule from degeneration and acute ischemic injury. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 5. pp. 902-913.
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