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Relationship between PI3K/mTOR/RhoA pathway-regulated cytoskeletal rearrangements and phagocytic capacity of

H R Bao1, J L Chen1, F Li1

  • 1Department of Gerontal Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas
|June 11, 2020
PubMed

Insights

The PI3K/mTOR/RhoA pathway regulates macrophage phagocytosis by altering cell structure. Inhibiting PI3K reduces phagocytic capacity, while inhibiting mTOR enhances it, impacting cytoskeletal rearrangements.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Signaling

Background:

  • Phagocytosis is a critical immune process mediated by macrophages.
  • Cytoskeletal dynamics are essential for phagocytic function.
  • The PI3K/mTOR/RhoA signaling pathway is implicated in cell motility and structure.

Purpose of the Study:

  • To investigate the role of PI3K/mTOR/RhoA signaling in regulating macrophage cytoskeletal rearrangements.
  • To determine the impact of this pathway on the phagocytic capacity of macrophages.

Main Methods:

  • RAW264.7 macrophages were transfected with PI3K-RNAi or mTOR-RNAi.
  • Gene silencing efficiencies were confirmed via mRNA and protein expression analysis.
  • Cytoskeletal morphology was assessed using microscopy.
  • Phagocytic capacity against Escherichia coli was quantified using mean fluorescence intensity (MFI) and percent phagocytosis.

Main Results:

  • PI3K-RNAi led to stiffened morphology and reduced phagocytosis.
  • mTOR-RNAi resulted in altered cell shape with increased filopodia and enhanced phagocytosis.
  • PI3K/mTOR/RhoA expression levels correlated with observed morphological and functional changes.
  • PI3K levels positively correlated with mTOR and RhoA, while mTOR negatively correlated with RhoA.

Conclusions:

  • The PI3K/mTOR/RhoA signaling pathway critically regulates macrophage phagocytic capacity through modulation of cytoskeletal rearrangements.
  • Differential roles of PI3K and mTOR in this pathway suggest distinct mechanisms influencing phagocytosis.

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