title: Class I HDACs specifically regulate E-cadherin expression in human renal epithelial cells.
abstract: 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.
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Sin Y
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Hae J
authors.initials: HJ
authors.lastname: Kee
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurz
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Finn K
authors.initials: FK
authors.lastname: Hansen
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Yuhee
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Gwi R
authors.initials: GR
authors.lastname: Kim
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Ming Q
authors.initials: MQ
authors.lastname: Lin
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.|Jilin Hospital Affiliated with Jilin University, Jilin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.|The Second Hospital of Jilin University, Changchun, China.
authors.forename: Zhe H
authors.initials: ZH
authors.lastname: Piao
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Myung H
authors.initials: MH
authors.lastname: Jeong
mesh_terms: D015703:Antigens, CD; D001549:Benzamides / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D011725:Pyridines / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D001549:Benzamides; D015415:Biomarkers; C513384:CDH1 protein, human; D015820:Cadherins; D016326:Extracellular Matrix Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; C529435:PCI 34051; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C118739:entinostat; C012589:trichostatin A; D006655:Histone Deacetylases
keywords: E-cadherin; HK-2 cells; class I HDAC; epithelial-mesenchymal transition (EMT); renal fibrosis