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The Role of CXCL13 in GC-1 Cell Cycle Arrest Induced by Titanium Dioxide Nanoparticles Through JAK2/STAT3 Signaling

Yuzhu Lei1, Ruoyun Dong2, Chenhao Sun1

  • 1Department of Preventive Medicine/the Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, School of Medicine, Shihezi University, Shihezi, Xinjiang, China.

Journal of Applied Toxicology : JAT
|January 8, 2025
PubMed

Insights

Titanium dioxide nanoparticles (TiO2 NPs) cause cell cycle arrest in mouse spermatogonia by downregulating CXCL13, which inhibits the JAK2/STAT3 pathway. Restoring CXCL13 can reverse these effects.

Area of Science:

  • Toxicology
  • Cell Biology
  • Molecular Biology

Background:

  • Titanium dioxide nanoparticles (TiO2 NPs) are known to induce cell cycle arrest in spermatogonia.
  • The JAK2/STAT3 signaling pathway is crucial for cell cycle progression, but its upstream regulation by TiO2 NPs is not fully understood.

Purpose of the Study:

  • To investigate if CXCL13 regulates the JAK2/STAT3 signaling pathway in TiO2 NP-induced cell cycle arrest in mouse spermatogonia (GC-1 cells).

Main Methods:

  • GC-1 cells were exposed to varying concentrations of TiO2 NPs.
  • Cell viability, cell cycle distribution, protein levels (CXCL13, JAK2/STAT3 pathway proteins, cell cycle regulators), and signaling pathway activation were analyzed.
  • Recombinant CXCL13 protein was used to confirm its role.

Main Results:

  • TiO2 NPs reduced cell viability and induced G0/G1 phase cell cycle arrest, decreasing Cyclin D1, CDK4, Cyclin E1, CDK2, and increasing p21.
  • TiO2 NPs inhibited CXCL13 protein levels and weakened JAK2/STAT3 pathway activation (reduced p-JAK2/JAK2 and p-STAT3/STAT3).
  • Exogenous CXCL13 counteracted TiO2 NP-induced suppression of the JAK2/STAT3 pathway and G0/G1 cell cycle arrest.

Conclusions:

  • TiO2 NPs induce cell cycle arrest in GC-1 cells by downregulating CXCL13, subsequently inhibiting the JAK2/STAT3 signaling pathway.
  • This study elucidates a novel mechanism of TiO2 NP toxicity, highlighting the role of the CXCL13/JAK2/STAT3 axis in spermatogonial cell cycle regulation.
Keywords:
CXCL13GC‐1 cellsJAK2/STAT3 signaling pathwaycell cycle arresttitanium dioxide nanoparticles

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