HBV promotes the proliferation of hepatic stellate cells via the PDGF-B/PDGFR-β signaling pathway in vitro

被引:71
作者
Bai, Qixuan [1 ]
An, Jing [2 ]
Wu, Xiaoning [1 ]
You, Hong [1 ]
Ma, Hong [1 ]
Liu, Tianhui [1 ]
Gao, Na [2 ]
Jia, Jidong [1 ]
机构
[1] Capital Med Univ, Liver Res Ctr, Beijing Friendship Hosp, Beijing 100050, Peoples R China
[2] Capital Med Univ, Sch Basic Med Sci, Dept Microbiol, Beijing 100050, Peoples R China
基金
国家高技术研究发展计划(863计划); 中国国家自然科学基金;
关键词
hepatitis B virus; hepatic stellate cells; liver fibrosis; platelet-derived growth factor; FAT-STORING CELLS; GROWTH FACTOR-BB; LIVER FIBROSIS; KINASE INHIBITOR; RECEPTOR-BETA; VIRUS; EXPRESSION; ACTIVATION; FIBROGENESIS; ALPHA;
D O I
10.3892/ijmm.2012.1148
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
The activation of hepatic stellate cells (HSCs) is closely associated with liver fibrosis in chronic hepatitis B virus (HBV) infection. However, the molecular mechanisms leading to HSC activation remain unclear. It has been reported that the platelet-derived growth factor-B (PDGF-13)/PDGF receptor-beta (PDGFR-beta) signaling pathway is involved in this process. Thus, we investigated whether HBV and its protein contribute to HSC proliferation by the PDGF-B/PDGFR-beta signaling pathway. HBV particles were purified from the supernatant of HepG2.2.15 cells by ultracentrifugation and the cell lines carrying HBV preS, e, c or x genes were obtained. After incubation with HBV particles or co-cultured with the cell lines expressed in the viral protein, the proliferation of LX-2 cells, an HSC cell line, were detected by flow cytometry and real-time PCR and the expression of molecules related to the PDGF-B/PDGFR-beta signaling pathway were further measured. Our results indicated that HBV particles, c and x proteins promoted LX-2 proliferation and increased the mRNA levels of PDGF-B, PDGFR-beta, collagen-1 and alpha-smooth muscle actin (alpha-SMA), as well as the phosphorylation of PDGFR-beta; however, the expression protein levels of PDGF-B and PDGFR-beta remained unchanged. In conclusion, HBV particles and HBV c and x proteins promote HSC proliferation and fibrogenesis in vitro and the PDGF-beta/PDGFR-beta signaling pathway is important in this process.
引用
收藏
页码:1443 / 1450
页数:8
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