title: Epigenetic regulation of Thy-1 gene expression by histone modification is involved in lipopolysaccharide-induced lung fibroblast proliferation.
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 TLR4 gene. Our studies indicate that epigenetic regulation of Thy-1 gene expression by histone modification is involved in LPS-induced lung fibroblast proliferation.
authors.affiliation: Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: He
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Wang
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Deng
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Yongming
authors.initials: Y
authors.lastname: Chen
authors.forename: Shunpeng
authors.initials: S
authors.lastname: Xing
authors.forename: Xianyuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Jia
authors.initials: J
authors.lastname: Ding
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000107:Acetylation; D000818:Animals; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D018800:Thy-1 Antigens / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
chemical_list: D006657:Histones; D008070:Lipopolysaccharides; D018800:Thy-1 Antigens; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D004247:DNA