Open AccessClass I HDAC s specifically regulate E‐cadherin expression in human renal epithelial cells
Author(s) -
Choi Sin Y.,
Kee Hae J.,
Kurz Thomas,
Hansen Finn K.,
Ryu Yuhee,
Kim Gwi R.,
Lin Ming Q.,
Jin Li,
Piao Zhe H.,
Jeong Myung H.
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12919
Subject(s) - trichostatin a , histone deacetylase , fibronectin , extracellular matrix , gene knockdown , chemistry , transforming growth factor , small interfering rna , microbiology and biotechnology , cadherin , cancer research , histone deacetylase 5 , epithelial–mesenchymal transition , transfection , biology , downregulation and upregulation , histone , cell , biochemistry , apoptosis , gene
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 HDAC s or class‐selective HDAC s 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 HDAC s ( HDAC 1, 2, 3 and 8). Trichostatin A ( TSA ), MS 275, PCI 34051 and LMK 235 inhibited ECM proteins such as collagen type I or fibronectin in transforming growth factor β1 ( TGF ‐β1)‐induced HK 2 cells. However, restoration of TGF ‐β1‐induced E‐cadherin down‐regulation was only seen in HK ‐2 cells treated with TSA or MS 275, but not with PCI 34051, 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 HDAC 8, but not against other class I HDAC s ( HDAC 1, 2 and 3). E‐cadherin regulation is mediated by HDAC 8 expression, but not by HDAC 8 enzyme activity. Thus, class I HDAC s ( HDAC 1, 2, 3 and 8) play a major role in regulating ECM and EMT , whereas class II a HDAC s ( HDAC 4 and 5) are less effective.