Prominent fibroblast growth factor 21 with less abundant tumor-associated macrophages in hepatic mass of the conditional mgmt-deleted mice using LysM-Cre system
Issued Date
2025-12-01
Resource Type
ISSN
10233830
eISSN
1420908X
Scopus ID
2-s2.0-105012927049
Journal Title
Inflammation Research
Volume
74
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Inflammation Research Vol.74 No.1 (2025)
Suggested Citation
Sontidejkul S., Phuengmaung P., Saisorn W., Kaewduangduen W., Doi K., Boonmee A., Benjaskulluecha S., Palaga T., Leelahavanichkul A. Prominent fibroblast growth factor 21 with less abundant tumor-associated macrophages in hepatic mass of the conditional mgmt-deleted mice using LysM-Cre system. Inflammation Research Vol.74 No.1 (2025). doi:10.1007/s00011-025-02077-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111710
Title
Prominent fibroblast growth factor 21 with less abundant tumor-associated macrophages in hepatic mass of the conditional mgmt-deleted mice using LysM-Cre system
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Fibroblast growth factor 21 is a molecule responsible for cell energy regulation, mainly produced from hepatocytes, while O6-methylguanine-DNA methyltransferase is a mandatory enzyme for DNA repair. Methods: Because tumors in the livers might enhance hepatocytic FGF-21 production for supporting tumor-associated macrophages (TAM) to promote cancers, the intrahepatic tumor injection model was performed. Results: Indeed, intrahepatic injection of MC38 cells in wild-type mice increased FGF-21 in serum and liver tissue. Murine hepatocytes excreted FGF-21 after induction by cell stresses, lipopolysaccharide, and MC38 supernatant, while human hepatocytes (HepG2) produced FGF-21 after incubation with the conditioned media of CaCO<inf>2</inf>, but neither HK2 nor H292. Intrahepatic MC38 injection in mgmt null mice demonstrated a lower tumor size and intratumoral TAM (CD206-positive cells) but higher FGF-21 production when compared with intrahepatic tumors in mgmt control. Additionally, MC38 supernatant induced M2-like polarization, which was enhanced by recombinant FGF-21. Furthermore, TAM induction by MC38 supernatant caused cell stresses only in mgmt null macrophages but not in mgmt control cells, as indicated by increased cell-free DNA and malondialdehyde with reduced maximal respiration. The TAM transformation-induced cell injury was neutralized by recombinant FGF-21. Conclusion: TAM transformation in mgmt null macrophages induced more severe cell injuries than mgmt control macrophages, leading to the less abundant intratumoral TAM and increased FGF-21 to attenuate the injuries in mgmt null mice with tumors. Further studies on FGF-21 and MGMT in cancers are interesting.