2. Academic Validation
  3. FNDC5 induces M2 macrophage polarization and promotes hepatocellular carcinoma cell growth by affecting the PPARγ/NF-κB/NLRP3 pathway

FNDC5 induces M2 macrophage polarization and promotes hepatocellular carcinoma cell growth by affecting the PPARγ/NF-κB/NLRP3 pathway

  • Biochem Biophys Res Commun. 2021 Dec 10;582:77-85. doi: 10.1016/j.bbrc.2021.10.041.
Huayuan Liu 1,  Mengya Wang 2,  Zhipeng Jin 3,  Dongxu Sun 3,  Ting Zhu 4,  Xinyue Liu 3,  Xueying Tan 5,  Guangjun Shi 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, China.
  • 2 Department of Physiology, School of Basic Medicine, Qingdao University, China.
  • 3 Graduate School of Dalian Medical University, China.
  • 4 Department of Gynecology, The Affiliated Qingdao Municipal Hospital of Qingdao University, China.
  • 5 Department of Laboratory, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China. Electronic address: [email protected].
  • 6 Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, China. Electronic address: [email protected].
PMID: 34695754 DOI: 10.1016/j.bbrc.2021.10.041
Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: We preliminarily demonstrated that FNDC5 in hepatocellular carcinoma cells promotes the polarization of M2 macrophages by affecting the PPARγ/NF-κB/NLRP3 pathway.

Keywords

FNDC5; Hepatocellular carcinoma; M1/M2 polarization; Macrophage; Peroxisome proliferator-activated receptor γ.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.87%, PPARγ Antagonist