Document Detail

Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury.
MedLine Citation:
PMID:  17641247     Owner:  NLM     Status:  MEDLINE    
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.
Naohiko Imai; Keiichi Hishikawa; Takeshi Marumo; Junichi Hirahashi; Toshihiko Inowa; Yumi Matsuzaki; Hideyuki Okano; Tadaichi Kitamura; David Salant; Toshiro Fujita
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-07-19
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  25     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-08     Completed Date:  2007-12-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2469-75     Citation Subset:  IM    
Department of Clinical Renal Regeneration, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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MeSH Terms
Acetylation / drug effects
Disease Progression
Gene Expression Regulation / drug effects
Glomerulonephritis / drug therapy*,  etiology,  metabolism
Glomerulosclerosis, Focal Segmental / drug therapy*,  etiology,  metabolism
Hematopoietic Stem Cells / drug effects*,  metabolism
Histone Deacetylase Inhibitors*
Histones / metabolism
Hydroxamic Acids / pharmacology*,  therapeutic use
Kidney / cytology*
Mice, Inbred C57BL
Multipotent Stem Cells / drug effects*,  metabolism
Nephritis, Interstitial / drug therapy,  etiology,  metabolism,  prevention & control
Protein Processing, Post-Translational / drug effects
Sheep / blood
Specific Pathogen-Free Organisms
Transcription Factors / biosynthesis,  genetics
Grant Support
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Histones; 0/Hydroxamic Acids; 0/Msc protein, mouse; 0/Transcription Factors; 58880-19-6/trichostatin A

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