FAM19A3, a novel secreted protein, modulates the microglia/macrophage polarization dynamics and ameliorates cerebral

Yankun Shao1, Ting Deng2, Tong Zhang3

  • 1Neurology Department, China-Japan Union Hospital, Jilin University, Changchun 130031, China.

FEBS Letters
|January 18, 2015
PubMed

Insights

Researchers found that FAM19A3, a novel secreted protein, promotes M2 polarization in microglia and macrophages. This finding suggests FAM19A3 may be a therapeutic target for mitigating cerebral ischemia.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Microglia play a crucial role in the brain's immune response, with distinct M1 (pro-inflammatory) and M2 (anti-inflammatory/repair) phenotypes.
  • Microglial polarization is critical in the pathogenesis and resolution of cerebral ischemia.
  • The specific molecular regulators of microglial polarization in stroke remain incompletely understood.

Purpose of the Study:

  • To identify novel genes and secreted proteins involved in microglial activation during cerebral ischemia.
  • To investigate the role of the identified gene, FAM19A3, in regulating microglial polarization.
  • To evaluate the therapeutic potential of FAM19A3 in a mouse model of cerebral ischemia.

Main Methods:

  • Utilized the middle cerebral artery occlusion (MCAO) mouse model to induce cerebral ischemia.
  • Analyzed gene expression in microglia, identifying FAM19A3 as significantly upregulated.
  • Administered recombinant FAM19A3 in vitro and in vivo to assess its effects on microglial and macrophage polarization.
  • Evaluated the impact of FAM19A3 on neurological deficits and infarct volume in the MCAO model.

Main Results:

  • FAM19A3 was significantly upregulated in microglia from MCAO mice.
  • M2 stimuli promoted FAM19A3 expression and secretion, suggesting it is an M2-type gene.
  • Recombinant FAM19A3 promoted M2 polarization and inhibited M1 polarization of microglia and macrophages in vitro and in vivo.
  • FAM19A3 administration attenuated cerebral ischemia in the MCAO mouse model.

Conclusions:

  • FAM19A3 is a novel secreted protein that modulates microglia/macrophage polarization dynamics.
  • FAM19A3 promotes an M2-like phenotype, shifting the balance away from pro-inflammatory M1 responses.
  • FAM19A3 demonstrates therapeutic potential for ameliorating cerebral ischemia by influencing neuroinflammation.

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