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Activation of Nrf2 signalling pathway by tectoridin protects against ferroptosis in particulate matter-induced lung

Tingting Dong1, Xiaoye Fan1, Nan Zheng2

  • 1Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China.

British Journal of Pharmacology
|April 3, 2023
PubMed
Abstract

Insights

Tectoridin protects against PM2.5 lung injury by activating the Nrf2 pathway, which inhibits ferroptosis. This highlights tectoridin

Area of Science:

  • Environmental toxicology
  • Cellular and molecular toxicology
  • Respiratory medicine

Background:

  • Ferroptosis is implicated in particulate matter 2.5 (PM2.5)-induced lung injury.
  • The Nrf2 signaling pathway's role in mitigating PM2.5-induced lung injury requires further elucidation.

Purpose of the Study:

  • To investigate the protective mechanism of the Nrf2 signaling pathway against PM2.5-induced lung injury.
  • To evaluate the therapeutic potential of tectoridin, a bioactive molecule, in ameliorating PM2.5-induced lung injury by modulating ferroptosis.

Main Methods:

  • Utilized Nrf2-knockout (KO) mice and Nrf2 siRNA in Beas-2b cells to examine Nrf2's regulatory effect on ferroptosis.
  • Assessed the in vitro and in vivo effects and mechanisms of tectoridin on PM2.5-induced lung injury.
  • Evaluated lung injury using histological staining (HE, PAS) and measured inflammatory factors, lipid peroxidation, iron accumulation, and ferroptosis markers (MDA, GSH, GPX4, xCT).

Main Results:

  • Nrf2 deletion exacerbated PM2.5-induced lung injury, iron accumulation, and ferroptosis.
  • Tectoridin activated Nrf2 target genes, preventing PM2.5-induced cell death, lipid peroxidation, and iron accumulation.
  • Tectoridin's protective effects against ferroptosis and lung injury were significantly diminished in Nrf2-deficient models (siNrf2 and Nrf2-KO mice).

Conclusions:

  • Nrf2 activation protects against PM2.5-induced lung injury by inhibiting ferroptosis-mediated lipid peroxidation.
  • Tectoridin demonstrates significant therapeutic potential for treating PM2.5-induced lung injury via the Nrf2/ferroptosis pathway.
Keywords:
Nrf2ferroptosisparticulate matter-induced lung injurytectoridin

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