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HBx基因通过ERK1/2信号通路促肝细胞增殖及炎性因子表达
HBx gene accelerates cell proliferation and enhances inflammatory factors expression through ERK1/2 signaling pathway
- 第三军医大学学报 2020年42卷第8期 页码：790-798
- 作者机构：
- 作者简介：
- 基金信息：国家自然科学基金面上项目(81071770)
DOI：10.16016/j.1000-5404.201910164
中图分类号：收稿：2019-10-24，
纸质出版：2020-04-30
- 稿件说明：
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黄欣, 张思遥, 王薛, 等. HBx基因通过ERK1/2信号通路促肝细胞增殖及炎性因子表达[J]. 第三军医大学学报, 2020,42(8):790-798.
Xin HUANG, Siyao ZHANG, Xue WANG, et al. HBx gene accelerates cell proliferation and enhances inflammatory factors expression through ERK1/2 signaling pathway[J]. Journal of Third Military Medical University, 2020, 42(8): 790-798.
黄欣, 张思遥, 王薛, 等. HBx基因通过ERK1/2信号通路促肝细胞增殖及炎性因子表达[J]. 第三军医大学学报, 2020,42(8):790-798. DOI： 10.16016/j.1000-5404.201910164.
Xin HUANG, Siyao ZHANG, Xue WANG, et al. HBx gene accelerates cell proliferation and enhances inflammatory factors expression through ERK1/2 signaling pathway[J]. Journal of Third Military Medical University, 2020, 42(8): 790-798. DOI： 10.16016/j.1000-5404.201910164.
摘要
Abstract
Objective
2
To investigate the effects of HBx gene on hepatocyte cycle and immune system
in vivo
based on self-developed mouse model with stable expression of HBx gene.
Methods
2
Lentivirus carrying HBx gene were used to infect liver precursor cells 14-19. Then the modified liver precursor cells were injected into the portal vein of mice to construct the model. The model was identified with qRT-PCR
Western blot assay and immunohistochemistry. In 180 d after the model establishment
the mRNA and protein levels of cell cycle regulators CDK4 and Cyclin D1
TNF-α and IL-10 in the liver tissue were detected. While the protein levels of the proteins in the ERK1/2 and MEK1/2 signalling pathways were also measured. HE staining was used to observe the pathological changes in the liver tissue.
Results
2
The mouse model with stable expression of HBx gene was successfully constructed. Compared with the mice of normal saline group and the EGFP-14-19 group
in the mice in 180 d after the model establishment
HBx significantly up-regulated the mRNA (
P
<
0.01) and protein levels of CDK4
Cyclin D1 and TNF-α
but down-regulated the expression of IL-10 at both levels (
P
<
0.05). HBx significantly activated ERK1/2 signalling pathway. After the administration of ERK1/2 signal pathway inhibitor U0126
the mRNA and protein expression of CDK4
Cyclin D1
and TNF-α was significantly down-regulated in the experimental group than the control group (
P
<
0.05)
but the mRNA and protein levels of IL-10 were in an opposite trend (
P
<
0.01). HE staining showed that the liver tissue had obvious pathological changes in the mouse model.
Conclusion
2
HBx accelerates cell proliferation and induces liver inflammation by activating ERK1/2 signaling pathway.
关键词
Keywords
references
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