Differential regulation of connective tissue growth factor in renal cells by histone deacetylase inhibitors

Abstract

Introduction Post-translational modifications of histone proteins affect chromatin organization, among them acetylation and deacetylation of the N-terminal tails of the core histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) [1]

Epigenetic regulation of myofibroblast differentiation and extracellular matrix production in nasal polyp‐derived fibroblasts

“…We showed that expression levels of HDAC2, α‐SMA and TGF‐β1 are increased in nasal polyp tissues, which suggested that HDAC2 regulates myofibroblast differentiation and plays a role in nasal polyp formation. Several recent studies have suggested that TSA, an HDAC inhibitor, suppresses myofibroblast differentiation in hepatic stellate cells , skin fibroblasts , kidney cells , lung fibroblasts and corneal fibroblasts . In this study, we demonstrated that TSA inhibits TGF‐β1‐induced morphological changes, myofibroblast differentiation and ECM accumulation in NPDFs.…”

“…According to recent findings, trichostatin A (TSA), an inhibitor of HDACs, abrogates TGF‐β1‐induced ECM expression in renal , skin , cornea , liver and lung fibrosis tissues. However, the effects of TSA inhibition on myofibroblast differentiation in nasal polyposis have not yet been reported.…”

HDAC inhibitors in experimental liver and kidney fibrosis

“…The expression of CTGF in renal endothelial and epithelial cells can be influenced by HDAC inhibitors [141-143]. Interestingly, the expression of CTGF was differentially regulated by different HDAC inhibitors.…”

“…Interestingly, the expression of CTGF was differentially regulated by different HDAC inhibitors. CTGF was clearly up-regulated when endothelial cells were incubated with TSA, sodium butyrate and SAHA, nevertheless VPA was found to be less effective [141]; while in epithelial cells, CTGF expression was dependent on culture confluency and donor variability [142,143]. …”

Connective tissue growth factor: Context‐dependent functions and mechanisms of regulation

“…In our own studies, we observed cell type dependent regulation of CTGF by HDAC inhibitors. CTGF was strongly upregulated in several types of endothelial cells, while in renal epithelial cell lines CTGF gene expression was reduced or remained unaltered upon treatment with HDAC inhibitors [109]. These data indicate that, in addition to the acetylation status of the histones, CTGF expression will be determined by cell type‐specific transcription factors, which are direct or indirect targets of HDACs.…”