当前位置： SCI文献检索 > JOURNAL OF CELLULAR BIOCHEMISTRY期刊下所有文献 > Thrombin Induces CCL2 Expression in Human Lung Fibroblasts via p300 Mediated Histone Acetylation and NF-KappaB Activation.

Thrombin Induces CCL2 Expression in Human Lung Fibroblasts via p300 Mediated Histone Acetylation and NF-KappaB Activation.

Abstract：

:Thrombin has been shown to play a key role in lung diseases such as pulmonary fibrosis via the induction of fibrotic cytokine- chemokine (CC motif) ligand-2 (CCL2) expression. We previously reported that transcription factor nuclear factor-κB (NF-κB) is responsible for thrombin-induced CCL2 expression in human lung fibroblasts (HLFs). Here, we extended our study to investigate the epigenetic regulation mechanism for thrombin-induced CCL2 expression in HLFs. HLFs were cultured in F-12 medium. CCL2 protein and mRNA levels were detected by ELISA and quantitative real-time PCR, respectively. Histone, histone acetyltransferases, and NF-κB binding to CCL2 promoter were detected by ChIP assay. NF-κB activation was detected by Western blotting. We revealed that increased binding of histone acetyltransferase p300 and acetylated histone H3 and H4 to CCL2 promoter are responsible for thrombin induced CCL2 expression in HLF cells. In addition, p300 inhibition attenuates both thrombin induced-CCL2 expression and histone H3 and H4 acetylation in HLFs, suggesting that p300 is involved in thrombin-induced CCL2 expression via hyperacetylating histone H3 and H4. Our data further showed that p300 also regulates CCL2 expression via interaction with NF-κB p65, as depletion of p300 inhibits both NF-κB p65 activation and its binding to CCL2 promoter. The findings strongly suggest that epigenetic dysregulation and the interaction between histone acetyltransferase and transcription factor may be responsible for thrombin induced-CCL2 expression in HLFs. Increased understanding of the epigenetic mechanisms of CCL2 regulation may provide opportunities for identifying novel molecular targets for therapeutic purposes. J. Cell. Biochem. 118: 4012-4019, 2017. © 2017 Wiley Periodicals, Inc.

journal_name

J Cell Biochem

journal_title

Journal of cellular biochemistry

authors

Deng X,Zhou X,Deng Y,Liu F,Feng X,Yin Q,Gu Y,Shi S,Xu M

doi

10.1002/jcb.26057

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

4012-4019

issue

eissn

0730-2312

issn

1097-4644

journal_volume

118

pub_type

杂志文章

在线工具

Thrombin Induces CCL2 Expression in Human Lung Fibroblasts via p300 Mediated Histone Acetylation and NF-KappaB Activation.