Document Detail


Differential regulation of connective tissue growth factor in renal cells by histone deacetylase inhibitors.
MedLine Citation:
PMID:  19210579     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Regulation of the profibrotic and angiogenesis modulating cytokine connective tissue growth factor (CTGF) occurs primarily at the transcriptional level. Therefore, we hypothesized that histone deacetylating enzymes (HDAC), which modulate the accessibility of transcriptionally active promoter regions, might play a role in the regulation of CTGF gene expression. We analyzed microvascular endothelial cells, which showed immunoreactivity for acetylated histone in kidney sections, and compared them with renal tubular epithelial cells. Treatment of cultured endothelial cells with different HDAC inhibitors up-regulated CTGF mRNA and protein. Pre-treatment with HDAC inhibitors facilitated induction of CTGF by transforming growth factor-beta (TGF-beta) or lysophosphatidic acid. Transcription factors of the FoxO family were involved in the up-regulation of CTGF as shown at protein level and by reporter gene analyses. In tubular epithelial cells, up-regulation of CTGF was only observed when these cells were cultured as subconfluent cells. Dense cells, which are more likely to resemble tubular cells in vivo, showed no up-regulation upon treatment with HDAC inhibitors and were protected against CTGF induction by TGF-beta. Taken together, our data indicate that the effect of HDAC inhibitors on CTGF expression is largely cell dependent in non-tumour cells. Different cell type-specific transcription factors seem to determine whether CTGF expression is reduced or increased in cells exposed to HDAC inhibitors.
Authors:
Claudiu Komorowsky; Matthias Ocker; Margarete Goppelt-Struebe
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2009-2-04
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  13     ISSN:  1582-4934     ISO Abbreviation:  -     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2010-4-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  2353-2364     Citation Subset:  -    
Affiliation:
Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Loschgestrasse 8, D-91054 Erlangen, Germany.
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