Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury

Stem Cells. 2007 Oct;25(10):2469-75. doi: 10.1634/stemcells.2007-0049. Epub 2007 Jul 19.


Bone morphogenic protein (BMP)-7 is expressed in the adult kidney and reverses chronic renal injury when given exogenously. Here, we report that a histone deacetylase inhibitor, trichostatin A (TSA), attenuates chronic renal injury, in part, by augmenting the expression of BMP-7 in kidney side population (SP) cells. We induced accelerated nephrotoxic serum nephritis (NTN) in C57BL/6 mice and treated them with TSA for 3 weeks. Compared with vehicle-treated NTN mice, treatment with TSA prevented the progression of proteinuria, glomerulosclerosis, interstitial fibrosis, and loss of kidney SP cells. Basal gene expression of renoprotective factors such as BMP-7, vascular endothelial growth factor, and hepatocyte growth factor was significantly higher in kidney SP cells as compared with non-SP cells. Treatment with TSA significantly upregulated the expression of BMP-7 in SP cells but not in non-SP cells. Moreover, initiation of treatment with TSA after 3 weeks of NTN (for 3 weeks, until 6 weeks) partially but significantly reversed renal dysfunction. Our results indicate an important role of SP cells in the kidney as one of the possible generator cells of BMP-7 and TSA as a stimulator of the cells in reversing chronic renal disease. Disclosure of potential conflicts of interest is found at the end of this article.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Disease Progression
  • Gene Expression Regulation / drug effects
  • Glomerulonephritis / drug therapy*
  • Glomerulonephritis / etiology
  • Glomerulonephritis / metabolism
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / etiology
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Histone Deacetylase Inhibitors*
  • Histones / metabolism
  • Hydroxamic Acids / pharmacology*
  • Hydroxamic Acids / therapeutic use
  • Kidney / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / drug effects*
  • Multipotent Stem Cells / metabolism
  • Nephritis, Interstitial / drug therapy
  • Nephritis, Interstitial / etiology
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / prevention & control
  • Protein Processing, Post-Translational / drug effects
  • Sheep / blood
  • Specific Pathogen-Free Organisms
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Msc protein, mouse
  • Transcription Factors
  • trichostatin A