Therapeutic effects of histone deacetylase inhibitors on kidney disease

Arch Pharm Res. 2018 Feb;41(2):162-183. doi: 10.1007/s12272-017-0998-7. Epub 2017 Dec 11.

Abstract

Increasing evidence has shown the involvement of histone deacetylases (HDACs) in the development and progression of various renal diseases, highlighting its inhibition as a promising therapeutic strategy to prevent kidney diseases. Accordingly, numerous studies have shown that HDAC inhibitors protect the kidneys from various diseases through their effects on multiple pathways, such as suppression of transforming growth factor-β signaling pathway and nuclear factor-κB signaling pathways, augmentation of apoptosis, and inhibition of angiogenesis. To develop more effective and less toxic isoform-selective HDAC inhibitors and further improve clinical outcomes, it is necessary to identify and understand the mechanisms involved in the pathogenesis and progression of renal diseases. This review focuses on the roles of HDAC inhibitors and the mechanisms involved in their therapeutic effects in experimental models of kidney diseases including glomerulosclerosis, tubulointerstitial fibrosis, glomerular and tubulointerstitial inflammation, lupus nephritis, polycystic kidney disease, and renal cell carcinoma (RCC).

Keywords: Fibrosis; Histone deacetylase inhibitors; Inflammation; Renal cell carcinoma; TGF-β signaling pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism*
  • Humans
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Treatment Outcome

Substances

  • Histone Deacetylase Inhibitors
  • Histone Deacetylases