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The present study aimed to investigate the protective role of the Nrf2 signalling pathway and its bioactive molecule tectoridin in PM2.5\u2010induced lung injury by regulating ferroptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We examined the regulatory effect of Nrf2 on ferroptosis in PM2.5\u2010induced lung injury and Beas\u20102b cells using Nrf2\u2010knockout (KO) mice and Nrf2 siRNA transfection. The effects and underlying mechanisms of tectoridin on PM2.5\u2010induced lung injury were evaluated in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Nrf2 deletion increased iron accumulation and ferroptosis\u2010related protein expression in vivo and vitro, further exacerbating lung injury and cell death in response to PM2.5 exposure. Tectoridin activated Nrf2 target genes and ameliorated cell death caused by PM2.5. In addition, tectoridin prevented lipid peroxidation, iron accumulation and ferroptosis in vitro, but in siNrf2\u2010treated cells, these effects almost disappeared. In addition, tectoridin effectively mitigated PM2.5\u2010induced respiratory system damage, as evaluated by HE, PAS, and inflammatory factors. Tectoridin also augmented the antioxidative Nrf2 signalling pathway and prevented changes in ferroptosis\u2010related morphological and biochemical indicators, including MDA levels, GSH depletion and GPX4 and xCT downregulation, in PM2.5\u2010induced lung injury. However, the effects of tectoridin on ferroptosis and respiratory injury were almost abolished in Nrf2\u2010KO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our data proposed the protective effect of Nrf2 activation on PM2.5\u2010induced lung injury by inhibiting ferroptosis\u2010mediated lipid peroxidation and highlight the potential of tectoridin as a PM2.5\u2010induced lung injury treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16085","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T06:06:06Z","timestamp":1680501966000},"page":"2532-2549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Activation of Nrf2 signalling pathway by tectoridin protects against ferroptosis in particulate matter\u2010induced lung 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