Liu Huayuan, Wang Mengya, Jin Zhipeng, Sun Dongxu, Zhu Ting, Liu Xinyue, Tan Xueying, Shi Guangjun
Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, China.
Department of Physiology, School of Basic Medicine, Qingdao University, China.
Biochem Biophys Res Commun. 2021 Dec 10;582:77-85. doi: 10.1016/j.bbrc.2021.10.041. Epub 2021 Oct 19.
The purpose of this study was to investigate the effect of FNDC5 expression levels in hepatocellular carcinoma on the phenotypic changes of macrophages in tumor tissues.
In this study, we established an in vitro co-culture system of hepatocellular carcinoma cells and macrophages. Then we performed overexpression or knockdown of FNDC5 gene in hepatocellular carcinoma cells to observe the effect of changes in FNDC5 expression level on the phenotypic changes of THP-1 macrophages. And the conclusions obtained in the in vitro assay were further validated by a subcutaneous tumorigenic nude mice model.
Our findings suggest that elevated FNDC5 expression in hepatocellular carcinoma cells lead to an increased M2 phenotype and decreased M1 phenotype in macrophages. This effect may be achieved by elevating PPARγ levels in macrophages while decreasing NF-κB and NLRP3 levels. These changes could be reversed by using PPARγ inhibitors.
We preliminarily demonstrated that FNDC5 in hepatocellular carcinoma cells promotes the polarization of M2 macrophages by affecting the PPARγ/NF-κB/NLRP3 pathway.
本研究旨在探讨肝细胞癌中FNDC5表达水平对肿瘤组织中巨噬细胞表型变化的影响。
在本研究中，我们建立了肝癌细胞与巨噬细胞的体外共培养体系。然后，我们在肝癌细胞中过表达或敲低FNDC5基因，以观察FNDC5表达水平变化对THP-1巨噬细胞表型变化的影响。体外试验所得结论通过皮下致瘤裸鼠模型进一步验证。
我们的研究结果表明，肝癌细胞中FNDC5表达升高会导致巨噬细胞中M2表型增加而M1表型减少。这种作用可能是通过提高巨噬细胞中PPARγ水平，同时降低NF-κB和NLRP3水平来实现的。使用PPARγ抑制剂可逆转这些变化。
我们初步证明，肝癌细胞中的FNDC5通过影响PPARγ/NF-κB/NLRP3通路促进M2巨噬细胞极化。
