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

Naohiko Imai, Keiichi Hishikawa, Takeshi Marumo, Junichi Hirahashi, Toshihiko Inowa, Yumi Matsuzaki, Hideyuki Okano, Tadaichi Kitamura, David Salant, Toshiro Fujitaa

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2469-2475
Number of pages7
JournalStem Cells
Volume25
Issue number10
DOIs
Publication statusPublished - 2007 Oct

Keywords

  • Anti-glomerular basement membrane disease
  • Chronic renal failure
  • Side population
  • Stem cell
  • Transcription regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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