Class I HDACs specifically regulate E-cadherin expression in human renal epithelial cells

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• 作者：Sin Y. Choi ; Hae J. Kee ; Thomas Kurz ; Finn K. Hansen ; Yuhee Ryu ; Gwi R. Kim ; Ming Q. Lin ; Li Jin ; Zhe H. Piao and Myung H. Jeong
• 刊名：Journal of Cellular and Molecular Medicine
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：20
• 期：12
• 页码：2289-2298
• 全文大小：684K
• ISSN：1582-4934

文摘

Epithelial-mesenchymal transition (EMT) and renal fibrosis are closely involved in chronic kidney disease. Inhibition of histone deacetylase (HDAC) has an anti-fibrotic effect in various diseases. However, the pathophysiological role of isoform-specific HDACs or class-selective HDACs in renal fibrosis remains unknown. Here, we investigated EMT markers and extracellular matrix (ECM) proteins in a human proximal tubular cell line (HK-2) by using HDAC inhibitors or by knockdown of class I HDACs (HDAC1, 2, 3 and 8). Trichostatin A (TSA), MS275, PCI34051 and LMK235 inhibited ECM proteins such as collagen type I or fibronectin in transforming growth factor β1 (TGF-β1)-induced HK2 cells. However, restoration of TGF-β1-induced E-cadherin down-regulation was only seen in HK-2 cells treated with TSA or MS275, but not with PCI34051, whereas TGF-β1-induced N-cadherin expression was not affected by the inhibitors. ECM protein and EMT marker levels were prevented or restored by small interfering RNA transfection against HDAC8, but not against other class I HDACs (HDAC1, 2 and 3). E-cadherin regulation is mediated by HDAC8 expression, but not by HDAC8 enzyme activity. Thus, class I HDACs (HDAC1, 2, 3 and 8) play a major role in regulating ECM and EMT, whereas class IIa HDACs (HDAC4 and 5) are less effective.