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Updated: Sep 14, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

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Focal adhesion kinase acts on the PI3K/Akt/mTOR pathway to modulate wear particle-induced autophagy in macrophages

Yucheng Tu1, Baiqi Pan1, Xiaoyu Wu1

  • 1Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

International Immunopharmacology
|July 24, 2025
PubMed

Insights

Focal adhesion kinase (FAK) inhibits autophagy in macrophages after titanium particle exposure. Inhibiting FAK with PF573228 may prevent periprosthetic joint infection complications by restoring normal autophagy.

Area of Science:

  • Biomedical Engineering
  • Immunology
  • Orthopedic Surgery

Background:

  • Periprosthetic joint infection (PJI) is a severe complication following total hip arthroplasty (THA).
  • Impaired innate immunity, particularly macrophage dysfunction due to prosthesis wear particles, contributes to PJI.
  • The precise mechanisms of wear particle-induced macrophage autophagy defects remain largely unknown.

Purpose of the Study:

  • To investigate the role of focal adhesion kinase (FAK) in titanium (Ti) particle-induced autophagy in macrophages.
  • To explore the potential of FAK inhibition as a therapeutic strategy for PJI.

Main Methods:

  • In vitro studies using macrophages exposed to Ti particles.
  • Utilized FAK inhibitor PF573228 to assess its effect on autophagy.
  • Employed a mouse calvarial model to evaluate PF573228's in vivo efficacy.

Main Results:

  • FAK activation was found to inhibit early-stage Ti particle-induced autophagy through the PI3K/Akt/mTOR pathway.
  • PF573228 treatment partially restored autophagy.
  • In vivo, PF573228 prevented FAK-mediated autophagy suppression, reduced inflammation, and mitigated inflammatory osteolysis.

Conclusions:

  • FAK modulates Ti-induced autophagy in macrophages via the PI3K/Akt/mTOR pathway.
  • Targeting FAK with inhibitors like PF573228 could normalize macrophage autophagy post-implantation.
  • FAK inhibitors represent a potential novel therapeutic approach for preventing PJI and associated tissue damage.
Keywords:
AutophagyFocal adhesion kinaseMacrophagesPeriprosthetic joint infectionWear particles

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