FAM76B regulates PI3K/Akt/NF-κB-mediated M1 macrophage polarization by influencing the stability of PIK3CD mRNA

Juan Wang1,2, Xinyue Zhao1, Qizhi Wang1

  • 1Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, 199 South Chang'an Road, Xi'an, 710062, Shaanxi Province, People's Republic of China.

Insights

FAM76B protein inhibits M1 macrophage polarization, a key factor in inflammation. This discovery offers new therapeutic targets for inflammatory bowel disease (IBD) and related conditions.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Macrophage polarization is critical in inflammation, but the regulatory mechanisms are not fully understood.
  • M1 macrophages are pro-inflammatory, and their dysregulation is implicated in various diseases.

Purpose of the Study:

  • To investigate the role of FAM76B in macrophage polarization.
  • To elucidate the molecular mechanisms by which FAM76B influences M1 macrophage polarization.
  • To evaluate the therapeutic potential of targeting FAM76B in inflammatory bowel disease (IBD).

Main Methods:

  • Utilized Fam76b knockout U937 cell lines to assess M1 macrophage polarization.
  • Analyzed mRNA and protein levels of M1 macrophage markers.
  • Investigated the involvement of the PI3K/Akt/NF-κB signaling pathway.
  • Conducted in vivo studies using a mouse model of IBD.

Main Results:

  • Fam76b knockout significantly increased M1 macrophage polarization.
  • FAM76B expression was downregulated in M1 macrophages.
  • FAM76B stabilizes PIK3CD mRNA, regulating the PI3K/Akt/NF-κB pathway.
  • FAM76B demonstrated a protective effect against IBD in vivo by inhibiting M1 polarization.

Conclusions:

  • FAM76B acts as an inhibitor of M1 macrophage polarization through the PI3K/Akt/NF-κB pathway.
  • FAM76B plays a protective role in inflammatory bowel disease.
  • Targeting FAM76B may offer a novel therapeutic strategy for IBD and other inflammatory diseases.

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