Trichostatin A Inhibits Epithelial Mesenchymal Transition Induced byTGF-beta 1 in Airway Epithelium

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486516.do
DOI
10.1371/journal.pone.0162058
Title
Trichostatin A Inhibits Epithelial Mesenchymal Transition Induced byTGF-beta 1 in Airway Epithelium
Description
This work was supported by Korean Health Technology R&D Project,Ministry of Health & Welfare, Republic of Korea (HI15C1512), HML,https://www.htdream.kr/index.do and Basic Science Research Programthrough the National Research Foundation of Korea (NRF) funded by theMinistry of Science, ICT & Future Planning (NRF-2015R1C1A1A02037312),IHP, http://www.nrf.re.kr/nrf_tot_cms/index.jsp?pmi-sso-return2=none.The funders had no role in study design, data collectionr This study wassupported by a grant from the Korean Health Technology R&D Project,Ministry of Health & Welfare, Republic of Korea (HI15C1512) and BasicScience Research Program through the National Research Foundation ofKorea(NRF) funded by the Ministry of Science, ICT & Future Planning(NRF-2015R1C1A1A02037312)
abstract
Background and Objectives
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)-beta 1-induced EMT in airway epithelium and nasal tissue.
Materials and Methods
A549 cells, primary nasal epithelial cells (PNECs), or inferior nasal turbinate organ culture were exposed to TSA prior to stimulation with TGF-beta 1. Expression levels of E-cadherin, vimentin, fibronectin, a-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, alpha-SMA, HDAC2, and HDAC4 in TGF-beta 1-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-beta 1 altered mRNA and protein expression levels of EMT markers including E-cadherin, vimentin, fibronectin, alpha-SMA, slug, and snail in A549 cells. Inhibition and silencing of HDAC2 and HDAC4 by TSA and siRNA enhanced TGF-beta 1-induced EMT in A549 cells. TSA blocked the effect of TGF-beta 1 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-beta 1.
Conclusions
We showed that EMT is induced by TGF-beta 1 in airway epithelial cells and nasal tissue via activation of HDAC2 and HDAC4, and that inhibition of HDAC2 and HDAC4 by TSA reduces TGF-beta 1-induced EMT. This observation indicates that histone deacetylase inhibitors such as TSA could be potentia
provenance
Made available in Cube on 2018-09-28T16:09:42Z (GMT). No. of bitstreams: 0
language
English
author
Park, Il-Ho
Kang, Ju-Hyung
Shin, Jae-Min
Lee, Heung-Man
orcid
PARK, IL-HO/0000-0002-7011-6071
accessioned
2018-09-28T16:09:42Z
available
2018-09-28T16:09:42Z
issued
2017
citation
PLOS ONE(11): 8
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486516.do
Funder
과학기술정보통신부
Funding Program
개인기초연구(미래부)
Project ID
1711057099
Jurisdiction
Rep.of Korea
Project Name
Mechanism of tissue remodleing and disease recalcitration by endoplasmic reticulum stress in chronic rhinosinusitis
rights
openAccess
type
article


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