CTGF公司
纤维化
癌症研究
转染
小干扰RNA
下调和上调
生长因子
化学
生物
内分泌学
细胞生物学
医学
内科学
生物化学
基因
受体
作者
Hung Sheng Hua,Heng Ching Wen,Chih Ming Weng,Hong Sheng Lee,Bing Chang Chen,Chien-Huang Lin
标识
DOI:10.1186/s12929-021-00735-5
摘要
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.
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