Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells

Jing Liu, Man J. Livingston, Guie Dong, Chengyuan Tang, Yunchao Su, Guangyu Wu, Xiao Ming Yin, Zheng Dong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Histone deacetylase inhibitors (HDACi) have therapeutic effects in models of various renal diseases including acute kidney injury (AKI); however, the underlying mechanism remains unclear. Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy. In cultured renal proximal tubular cells, SAHA and TSA enhanced autophagy during cisplatin treatment. We further verified the protective effect of TSA against cisplatin-induced apoptosis in these cells. Notably, inhibition of autophagy by chloroquine or by autophagy gene 7 (Atg7) ablation diminished the protective effect of TSA. In mice, TSA increased autophagy in renal proximal tubules and protected against cisplatin-induced AKI. The in vivo effect of TSA was also abolished by chloroquine and by Atg7 knockout specifically from renal proximal tubules. Mechanistically, TSA stimulated AMPK and inactivated mTOR during cisplatin treatment of proximal tubule cells and kidneys in mice. Together, these results suggest that HDACi may protect kidneys by activating autophagy in proximal tubular cells.

Original languageEnglish (US)
Article number322
JournalCell Death and Disease
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2018

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trichostatin A
Histone Deacetylase Inhibitors
Autophagy
Acute Kidney Injury
Cisplatin
Proximal Kidney Tubule
Kidney
Chloroquine
Gene Knockout Techniques
AMP-Activated Protein Kinases
Therapeutic Uses
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells. / Liu, Jing; Livingston, Man J.; Dong, Guie; Tang, Chengyuan; Su, Yunchao; Wu, Guangyu; Yin, Xiao Ming; Dong, Zheng.

In: Cell Death and Disease, Vol. 9, No. 3, 322, 01.03.2018.

Research output: Contribution to journalArticle

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AU - Wu, Guangyu

AU - Yin, Xiao Ming

AU - Dong, Zheng

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