Lipopolysaccharide induces YAP expression and regulates macrophage polarization in liver tumor of mouse

doi:10.3877/cma.j.issn.2095-3232.2020.03.018

Abstract

Abstract:

Objective

To investigate the role of lipopolysaccharide (LPS) in inducing the expression of YAP and regulating the macrophage polarization in the mouse model of orthotopically implanted liver tumor.

Methods

The wild type (WT), YAP gene-knockout (YAP-HKO), YAP- WT C57BL/6 mouse liver tumor models were established. After the models were established, 4 WT mice were randomly selected and assigned into the LPS group and were administered intraperitoneally with LPS 5 mg/kg per day. Another 4 mice were allocated into the control group and were given intraperitoneally with equivalent amount of normal saline. To verify the effect of YAP, YAP-HKO mouse group (n=4) and YAP-WT littermate mouse group (n=4) were established. All mice in each group were sacrificed after feeding for 10 d. The volume of liver tumor was measured. The expression levels of YAP, Ki67, F4/80 and CD163 in liver tissues in LPS and control groups, and the expression of F4/80 and CD163 in liver tissues of YAP-HKO and YAP-WT mice were observed by immunohistochemistry. The phenotype of macrophages in the mouse liver tissues was analyzed by flow cytometry. Parameters between two groups were statistically compared by t test.

Results

The volume of liver tumor in LPS group was (2.50±0.79) cm³, significantly larger than (0.97±0.29) cm³ in control group (t=3.641, P<0.05). The liver tumor volume of YAP-HKO mice was (0.13±0.11) cm³, significantly smaller than (0.78±0.23) cm³ of YAP-WT mice (t=-5.100, P<0.05). The expression levels of YAP, Ki67, F4/80 and CD163 in the liver tissues in LPS group were higher than those in control group. The expression levels of F4/80 and CD163 in the liver tissues of YAP-HKO mice were lower compared with those of YAP-WT mice. The percentage of M2-type macrophages in the liver tissues in LPS group was (69±3)%, significantly higher than (45±4)% in the control group (t=9.768, P<0.05). The percentage of M2-type macrophages in the liver tissues of YAP-HKO mice was (54±4)%, significantly lower than (68±7)% of YAP-WT mice (t=-3.669, P<0.05).

Conclusions

In the mouse model of orthotopically implanted liver tumor, LPS can recruit macrophages and induce M2-type macrophage polarization to promote the tumor proliferation by up-regulating the expression of YAP.

Key words: Liver neoplasms, experimental, Lipopolysaccharides, Yes-associated protein (YAP), Macrophages, Mice

Qifa Zheng, Hua Li, Zenan Yuan, Linsen Ye, Shuguang Zhu, Long Xia. Lipopolysaccharide induces YAP expression and regulates macrophage polarization in liver tumor of mouse[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2020, 09(03): 283-288.

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Figures/Tables 4

References 20

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