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

研究成果: Article査読

48 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2469-2475
ページ数7
ジャーナルStem Cells
25
10
DOI
出版ステータスPublished - 2007 10月

ASJC Scopus subject areas

  • 分子医療
  • 発生生物学
  • 細胞生物学

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