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The HDAC inhibitor, vorinastat, prevents TGF‐β1 induced EMT and apoptosis in human renal proximal tubular cells
Author(s) -
Hussain Faryal,
Brimble Elise,
Dickhout Jeffrey G.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.705.13
Subject(s) - epithelial–mesenchymal transition , apoptosis , transforming growth factor , cancer research , histone deacetylase inhibitor , fibroblast , chemistry , cadherin , vimentin , microbiology and biotechnology , endocrinology , histone deacetylase , medicine , biology , cell , histone , cancer , in vitro , immunohistochemistry , biochemistry , metastasis , gene
Renal interstitial fibrosis is characterized by renal fibroblast proliferation. This process involves renal tubular epithelial cells adopting a fibroblast morphology through epithelial‐to‐mesenchymal transition (EMT). EMT produces phenotypic changes such as epithelial cell adherins junction loss and de novo α‐smooth muscle actin (SMA) expression. TGF‐ß1 has been shown to stimulate EMT. Identifying agents that inhibit TGF‐ß1 induced EMT may prevent patient progression towards chronic renal failure (CRF). Previous work from our laboratory has shown that 4‐phenylbuterate (4‐PBA), a histone deacetylase inhibitor (HDACi), inhibited EMT. In this study, we hypothesized that a broad spectrum HDACi, vorinastat, would inhibit TGF‐ß1 induced EMT and apoptosis in human proximal tubular epithelium (hPTE). We tested vorinastat and 4‐PBA on TGF‐ß1 induced EMT in hPTE. TGF‐ß1 induced EMT was inhibited by both 1mM 4‐PBA and 5μM vorinastat as shown by cadherin junction preservation and reduced de novo α‐SMA expression. Vorinastat was also shown to prevent TGF‐ß1‐induced decrease of E‐cadherin and increase of type I collagen transcript levels. Further, 4‐PBA and vorinastat inhibited TGF‐ß1 induced apoptosis in hPTE. These findings suggest that HDACi prevent EMT and apoptosis induced by TGFß1 and may reduce the progression of patients with chronic kidney disease towards CRF. Funding, CIHR OSO‐115895.