Epigenetic regulation of Thy-1 gene expression by histone modification is involved in lipopolysaccharide-induced lung fibroblast proliferation.
Epigenetic regulation of Thy-1 gene expression by histone modification is involved in lipopolysaccharide-induced lung fibroblast proliferation.
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DOI：
10.1111/j.1582-4934.2012.01659.x
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发表时间：
2013-01
影响因子：
5.3
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
He Z;Wang X;Deng Y;Li W;Chen Y;Xing S;Zhao X;Ding J;Gao Y
脂多糖（LPS）诱导的肺纤维化以肺成纤维细胞的异常增殖和激活为特征。胸腺细胞分化抗原1（Thy - 1）的表观遗传调控与导致细胞异常增殖的肺成纤维细胞表型转化相关。然而，目前尚不清楚Thy - 1表达的表观遗传调控是否为LPS诱导的肺成纤维细胞增殖所必需。为解决这一问题并更好地理解相关潜在机制，我们以小鼠肺成纤维细胞为模型，观察LPS刺激后Thy - 1表达及组蛋白去乙酰化的变化。结果显示，通过BrdU掺入法检测的细胞DNA合成在LPS刺激早期（24小时）受影响较小，但在LPS刺激48或72小时后显著增加。同时，通过实时荧光定量PCR和蛋白质免疫印迹法检测发现，肺成纤维细胞中Thy - 1的表达随LPS刺激时间的延长而降低，并在72小时时降至最低。我们还发现，LPS刺激的肺成纤维细胞中组蛋白H3或H4的乙酰化水平均下降。染色质免疫沉淀（ChIP）实验表明，LPS刺激下Thy - 1启动子区域的组蛋白H4乙酰化（Ace - H4）水平降低。此外，上述所有变化均可因Toll样受体4（TLR4）基因缺失而减弱。我们的研究表明，组蛋白修饰对Thy - 1基因表达的表观遗传调控参与了LPS诱导的肺成纤维细胞增殖过程。
Lipopolysaccharide (LPS)-induced pulmonary fibrosis is characterized by aberrant proliferation and activation of lung fibroblasts. Epigenetic regulation of thymocyte differentiation antigen 1 (Thy-1) is associated with lung fibroblast phenotype transformation that results in aberrant cell proliferation. However, it is not clear whether the epigenetic regulation of Thy-1 expression is required for LPS-induced lung fibroblast proliferation. To address this issue and better understand the relative underlying mechanisms, we used mouse lung fibroblasts as model to observe the changes of Thy-1 expression and histone deacetylation after LPS challenge. The results showed that cellular DNA synthesis, measured by BrdU incorporation, was impacted less in the early stage (24 hrs) after the challenge of LPS, but significantly increased at 48 or 72 hrs after the challenge of LPS. Meanwhile, Thy-1 expression, which was detected by real-time PCR and Western blot, in lung fibroblasts decreased with increased time after LPS challenge and diminished at 72 hrs. We also found that the acetylation of either histone H3 or H4 decreased in the LPS-challenged lung fibroblasts. ChIP assay revealed that the acetylation of histone H4 (Ace-H4) decreased in the Thy-1 promoter region in response to LPS. In addition, all the above changes could be attenuated by depletion of TLR4 gene. Our studies indicate that epigenetic regulation of Thy-1 gene expression by histone modification is involved in LPS-induced lung fibroblast proliferation.
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影响因子：
6.2
作者：
Sub, Hyeon-Sook;Choi, Shinyeop;Khattar, Pallavi;Choi, Namjong;Lee, Sunhee C.
通讯作者：
Lee, Sunhee C.
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
影响因子：
5
作者：
Gutierrez-Venegas, Gloria;Kawasaki-Cardenas, Perla;Maldonado-Frias, Silvia
通讯作者：
Maldonado-Frias, Silvia
影响因子：
20.3
作者：
Roger, Thierry;Lugrin, Jerome;Calandra, Thierry
通讯作者：
Calandra, Thierry
脂多糖三击方案诱导急性肺损伤引起的快速肺纤维化
影响因子：
3.2
作者：
Li, Hui;Du, Shaohui;Yao, Zhibin
通讯作者：
Yao, Zhibin