Open AccessEpigenetic regulation of Thy‐1 gene expression by histone modification is involved in lipopolysaccharide‐induced lung fibroblast proliferation
Author(s) -
He Zhengyu,
Wang Xiangrui,
Deng Yuxiao,
Li Wen,
Chen Yongming,
Xing Shunpeng,
Zhao Xianyuan,
Ding Jia,
Gao Yuan
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01659.x
Subject(s) - epigenetics , histone , fibroblast , biology , microbiology and biotechnology , acetylation , cancer research , histone h4 , dna methylation , gene expression , regulation of gene expression , gene , cell culture , genetics
Abstract 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 TLR 4 gene. Our studies indicate that epigenetic regulation of Thy‐1 gene expression by histone modification is involved in LPS ‐induced lung fibroblast proliferation.