HDAC is essential for epigenetic regulation of Thy-1 gene expression during LPS/TLR4-mediated proliferation of lung fibroblasts
HDAC is essential for epigenetic regulation of Thy-1 gene expression during LPS/TLR4-mediated proliferation of lung fibroblasts
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HDAC 对于 LPS/TLR4 介导的肺成纤维细胞增殖过程中 Thy-1 基因表达的表观遗传调控至关重要
DOI：
10.1038/labinvest.2015.97
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发表时间：
2015-07
影响因子：
5
通讯作者：
He Zhengyu
中科院分区：
文献类型：
--
作者：
Xing Shunpeng;Nie Fang;Xu Qiaoyi;Deng Yuxiao;Li Wen;Yang Zhongwei;Zhao Xianyuan;Zhu Ping;Wang Xiangrui;Gao Yuan;He Zhengyu
脂多糖（LPS）诱导的肺成纤维细胞增殖与胸腺细胞分化抗原 - 1（Thy - 1）基因表达的丧失密切相关，同时伴有Thy - 1基因启动子区域组蛋白H3和H4的去乙酰化。
Lipopolysaccharide (LPS)-induced proliferation of lung fibroblasts is closely correlated with loss of gene expression of thymocyte differentiation antigen-1 (Thy-1), accompanied with deacetylation of histones H3 and H4 at the Thy-1 gene promoter region; however, the mechanism remains enigmatic. We report here that LPS downregulates Thy-1 gene expression by activating histone deacetylases (HDACs) via Toll-like receptor 4 (TLR4) signaling. Treatment of primary cultured mouse lung fibroblasts with LPS resulted in significant upregulation of TLR4 and enhanced cell proliferation that was abolished by silencing TLR4 with lentivirus-delivered TLR4 shRNA. Interestingly, LPS increased the mRNA and protein levels of HDAC-4,-5, and-7, an effect that was abrogated by HDAC inhibitor trichostatin A (TSA) or TLR4-shRNA-lentivirus. Consistent with these findings, Ace-H3 and Ace-H4 were decreased by LPS that was prevented by TSA. Most importantly, chromosome immunoprecipitation (ChIP) analysis demonstrated that LPS decreased the association of Ace-H4 at the Thy-1 promoter region that was efficiently restored by pretreatment with TSA. Accordingly, LPS decreased the mRNA and protein levels of Thy-1 that was inhibited by TSA. Furthermore, silencing the Thy-1 gene by lentivirus-delivered Thy-1 shRNA could promote lung fibroblast proliferation, even in the absence of LPS. Conversely, overexpressing Thy-1 gene could inhibit lung fibroblast proliferation and reduce LPS-induced lung fibroblast proliferation. Our data suggest that LPS upregulates and activates HDACs through TLR4, resulting in deacetylation of histones H3 and H4 at the Thy-1 gene promoter that may contribute to Thy-1 gene silencing and lung fibroblast proliferation.
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影响因子：
--
作者：
Yasutake T;Wada H;Higaki M;Nakamura M;Honda K;Watanabe M;Ishii H;Kamiya S;Takizawa H;Goto H
通讯作者：
Goto H
影响因子：
5.8
作者：
Ni YF;Wang J;Yan XL;Tian F;Zhao JB;Wang YJ;Jiang T
通讯作者：
Jiang T
DOI：
10.1084/jem.20080001
发表时间：
2008-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Xia H;Diebold D;Nho R;Perlman D;Kleidon J;Kahm J;Avdulov S;Peterson M;Nerva J;Bitterman P;Henke C
通讯作者：
Henke C
DOI：
10.1096/fasebj.28.1_supplement.862.3
发表时间：
2014-04
期刊：
The FASEB Journal
影响因子：
--
作者：
V. Lopes;S. O. Oliveira Júnior;M. Cezar;R. Damatto;C. Bonomo;L. Pagan;A. Lima;M. Gomes;L. Zornoff;K. Okoshi;M. Okoshi;P. Martinez
通讯作者：
V. Lopes;S. O. Oliveira Júnior;M. Cezar;R. Damatto;C. Bonomo;L. Pagan;A. Lima;M. Gomes;L. Zornoff;K. Okoshi;M. Okoshi;P. Martinez
DOI：
10.1096/fasebj.28.1_supplement.695.4
发表时间：
2014-04
期刊：
The FASEB Journal
影响因子：
--
作者：
Atul D Joshi;N. Barabutis;G. Thangjam;Charalampos Birmpas;J. Catravas
通讯作者：
Atul D Joshi;N. Barabutis;G. Thangjam;Charalampos Birmpas;J. Catravas