Histone deacetylase 7 mediates endothelin-1-induced connective tissue growth factor expression in human lung fibroblasts through p300 and activator protein-1 activation.
J Biomed Sci
; 28(1): 38, 2021 May 19.
Article
em En
| MEDLINE
| ID: mdl-34011384
ABSTRACT
BACKGROUND:
Histone deacetylase (HDAC) inhibition was reported to ameliorate lung fibrosis in animal models. However, little is known about the underlying mechanism of HDAC7 in the regulation of CTGF production in lung fibroblasts.METHODS:
The role of HDAC7 in CTGF production caused by ET-1 stimulation in WI-38 cells (human lung fibroblast) was examined. We also evaluated the expression of HDAC7 in the lung of ovalbumin-induced airway fibrosis model. Statistical data were shown as mean ± standard error.RESULTS:
ET-1-stimulated CTGF and α-SMA expression was attenuated by small interfering (si)RNA interference of HDAC7. ET-1 promoted HDAC7 translocation from the cytosol to nucleus. ET-1-stimulated CTGF expression was reduced by the transfection of p300 siRNA. ET-1 induced an increase in p300 activity. Furthermore, the acetylation of c-Jun was time-dependently induced by ET-1 stimulation, which was reduced by transfection of either HDAC7 or p300 siRNA. Both transfection of HDAC7 and p300 siRNA suppressed the ET-1-increased activity of AP-1-luciferase. Moreover, the presence of HDAC7 was required for ET-1-stimulated formation of HDAC7, p300, and AP-1 complex and recruitment to the CTGF promoter region. In an ovalbumin-induced airway fibrosis model, the protein level of HDAC7 was increased in the lung tissue, and the distribution of HDAC7 was colocalized with α-SMA-positive cells in the subepithelial layer of the airway.CONCLUSIONS:
ET-1 activates HDAC7 to initiate AP-1 transcriptional activity by recruiting p300 and eventually promotes the production of CTGF. HDAC7 might play a vital role in airway fibrosis and have the potential to be developed as a therapeutic target.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Fator de Transcrição AP-1
/
Endotelina-1
/
Proteína p300 Associada a E1A
/
Fator de Crescimento do Tecido Conjuntivo
/
Histona Desacetilases
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article