Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury

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Abstract

Autophagy mediates bulk degradation and recycling of cytoplasmic constituents to maintain cellular homeostasis. In response to stress, autophagy is induced and may either contribute to cell death or serve as a cell survival mechanism. Very little is known about autophagy in renal pathophysiology. This study examined autophagy and its pathological role in renal cell injury using in vitro and in vivo models of ischemia - reperfusion. We found that hypoxia (1% O2) induced autophagy in cultured renal proximal tubular cells. Blockade of autophagy by 3-methyladenine or small-interfering RNA knockdown of Beclin-1 and ATG5 (two key autophagic genes) sensitized the tubular cells to hypoxia-induced apoptosis. In an in vitro model of ischemia - reperfusion, autophagy was not induced by anoxic (0% O2) incubation in glucose-free buffer, but was induced during subsequent recovery/reperfusion period. In this model, suppression of autophagy also enhanced apoptosis. In vivo, autophagy was induced in kidney tissues during renal ischemia - reperfusion in mice. Autophagy was not obvious during the ischemia period, but was significantly enhanced during reperfusion. Inhibition of autophagy by chloroquine and 3-methyladenine worsened renal ischemia/reperfusion injury, as indicated by renal function, histology, and tubular apoptosis. Together, the results demonstrated autophagy induction during hypoxic and ischemic renal injury. Under these pathological conditions, autophagy may provide a protective mechanism for cell survival.

Original languageEnglish (US)
Pages (from-to)1181-1192
Number of pages12
JournalAmerican Journal of Pathology
Volume176
Issue number3
DOIs
StatePublished - Mar 2010

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Autophagy
Reperfusion Injury
Kidney
Reperfusion
Ischemia
Apoptosis
In Vitro Techniques
Hypoxia
Cell Survival
Cell Hypoxia
Wounds and Injuries
Chloroquine
Recycling
Small Interfering RNA
Histology
Buffers
Homeostasis
Cell Death

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. / Jiang, Man; Liu, Kebin; Luo, Jia; Dong, Zheng.

In: American Journal of Pathology, Vol. 176, No. 3, 03.2010, p. 1181-1192.

Research output: Contribution to journalArticle

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