Trichostatin A Inhibits Epithelial Mesenchymal Transition Induced by TGF-β1 in Airway Epithelium

• Published in: PloS one Vol. 11; no. 8; p. e0162058
• Main Authors: Park, Il-Ho, Kang, Ju-Hyung, Shin, Jae-Min, Lee, Heung-Man
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.08.2016; Public Library of Science (PLoS)
• Subjects: A549 Cells; Actin; Allergies; Antibiotics; Asthma; Biology and Life Sciences; Bone; Cadherins - genetics; Cadherins - metabolism; Cancer; Cell adhesion & migration; Cell culture; Cell migration; Cells, Cultured; Chromatin; E-cadherin; Endoscopy; Epigenetics; Epithelial cells; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Epithelium; Extracellular matrix; Fibroblasts; Fibronectin; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Growth factors; HDAC2 protein; Histone deacetylase; Histone Deacetylase 2 - genetics; Histone Deacetylase 2 - metabolism; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Hospitals; Humans; Hydroxamic Acids - pharmacology; Inflammation; Inhibition; Markers; Medicine; Medicine and Health Sciences; Mesenchyme; mRNA; Muscles; Nose; Organ culture; Organ Culture Techniques; Otolaryngology; Polymerase chain reaction; Repressor Proteins - genetics; Repressor Proteins - metabolism; Research and Analysis Methods; Respiratory tract diseases; Rhinosinusitis; RNA, Messenger; siRNA; Smooth muscle; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Surgery; Transfection; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-a; Transforming growth factor-b1; Trichostatin A; Vimentin - genetics; Vimentin - metabolism; Western blotting; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162058

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. 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. 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. 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.