Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy

Mixuan Yi, Lei Zhang, Yu Liu, Man Jiang Livingston, Jiankang Chen, Norris Stanley Nahman, Fuyou Liu, Zheng Dong

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas inhibition of autophagy with chloroquine enhanced podocyte apoptosis during adriamycin treatment. To determine the role of autophagy in vivo, we established an inducible podocyte-specific autophagy-related gene 7 knockout mouse model (Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed higher levels of podocyte injury, glomerulopathy, and proteinuria during adriamycin treatment. Together, these observations support an important role of autophagy in protecting podocytes under the pathological conditions of glomerular disease, suggesting the therapeutic potential of autophagy induction.

Original languageEnglish (US)
Pages (from-to)F74-F84
JournalAmerican Journal of Physiology - Renal Physiology
Volume313
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Podocytes
Autophagy
Doxorubicin
Wounds and Injuries
Gene Knockout Techniques
Knockout Mice
Apoptosis
Chloroquine
Sirolimus
Proteinuria
Homeostasis

Keywords

  • Adriamycin
  • Apoptosis
  • Autophagy
  • Kidney
  • Podocytes
  • mTOR

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy. / Yi, Mixuan; Zhang, Lei; Liu, Yu; Livingston, Man Jiang; Chen, Jiankang; Nahman, Norris Stanley; Liu, Fuyou; Dong, Zheng.

In: American Journal of Physiology - Renal Physiology, Vol. 313, No. 1, 01.01.2017, p. F74-F84.

Research output: Contribution to journalArticle

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