title: Trichostatin A Inhibits Epithelial Mesenchymal Transition Induced by TGF-β1 in Airway Epithelium.
abstract: OBJECTIVE
  Tissue remodeling is believed to cause recalcitrant chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) is a novel clinical therapeutic target in many chronic airway diseases related with tissue remodeling. The aim of this study was to investigate the effect of trichostatin A (TSA) on transforming growth factor (TGF)-β1-induced EMT in airway epithelium and nasal tissue.
  
  
  METHODS
  A549 cells, primary nasal epithelial cells (PNECs), or inferior nasal turbinate organ culture were exposed to TSA prior to stimulation with TGF-β1. Expression levels of E-cadherin, vimentin, fibronectin, α-smooth muscle actin (SMA), histone deacetylase 2 (HDAC2), and HDAC4 were determined by western blotting and/or immunofluorescent staining. Hyperacetylation of histone H2 and H4 by TSA was measured by western blotting. After siHDAC transfection, the effects of HDAC2 and HDAC4 silencing on expression of E-cadherin, vimentin, fibronectin, α-SMA, HDAC2, and HDAC4 in TGF-β1-induced A549 were determined by RT-PCR and/or western blotting. We assessed the change in migration capacity of A549 cells by using cell migration assay and transwell invasion assay.
  
  
  RESULTS
  TGF-β1 altered mRNA and protein expression levels of EMT markers including E-cadherin, vimentin, fibronectin, α-SMA, slug, and snail in A549 cells. Inhibition and silencing of HDAC2 and HDAC4 by TSA and siRNA enhanced TGF-β1-induced EMT in A549 cells. TSA blocked the effect of TGF-β1 on the migratory ability of A549 cells. In experiments using PNECs and inferior turbinate organ cultures, TSA suppressed expression of EMT markers induced by TGF-β1.
  
  
  CONCLUSIONS
  We showed that EMT is induced by TGF-β1 in airway epithelial cells and nasal tissue via activation of HDAC2 and HDAC4, and that inhibition of HDAC2 and HDAC4 by TSA reduces TGF-β1-induced EMT. This observation indicates that histone deacetylase inhibitors such as TSA could be potential candidates for treatment of recalcitrant CRS related with tissue remodeling.
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors: Il-Ho
authors: http://orcid.org/0000-0002-7011-6071
authors: IH
authors: Park
authors: Department of Biomedical Sciences, Korea University Graduate School, Seoul, South Korea.
authors: Ju-Hyung
authors: JH
authors: Kang
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors: Jae-Min
authors: JM
authors: Shin
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Korea University Graduate School, Seoul, South Korea.|Medical Devices support Center, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors: Heung-Man
authors: HM
authors: Lee
mesh_terms: D000072283:A549 Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D005353:Fibronectins; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C012589:trichostatin A; C533423:HDAC2 protein, human; C400300:HDAC4 protein, human; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases