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• W3147160714 abstract "Abstract Fine particulate matter (PM 2.5 ) is an important component of air pollution and can induce lung inflammation and oxidative stress. We hypothesized that PM 2.5 could play a role in the induction of pulmonary fibrosis. We examined whether multiple intranasal instillation of PM 2.5 can induce pulmonary fibrosis in the mouse, and also investigated the underlying pro‐fibrotic signaling pathways. C57/BL6 mice were intranasally instilled with 50 μl of PM 2.5 suspension (7.8 μg/g body weight) or PBS three times a week over 3 weeks, 6 weeks or 9 weeks. To observe the recovery of pulmonary fibrosis after the termination of PM 2.5 exposure, 9 week‐PM 2.5 instilled mice were also studied at 3 weeks after termination of instillation. There were significant decreases in total lung capacity (TLC) and compliance (Cchord) in the 9‐week PM 2.5 ‐instilled mice, while there were increased histological fibrosis scores with enhanced type I collagen and hydroxyproline deposition, increased mitochondrial ROS levels and NOX activity, decreased total SOD and GSH levels, accompanied by decreased mitochondrial number and aberrant mitochondrial morphology (swelling, vacuolization, cristal disruption, reduced matrix density) in PM 2.5 ‐instilled mice. Multiple PM 2.5 instillation resulted in increased expression of TGFβ1, increases of N‐Cadherin and Vimentin and a decrease of E‐Cadherin. It also led to decreases in OPA1 and MFN2, and increases in Parkin, SQSTM1/p62, the ratio of light china (LC) 3B II to LC3B I, PI3k/Akt phosphorylation, and NLRP3 expression. Intranasal instillation of PM 2.5 for 9 weeks induced lung inflammation and pulmonary fibrosis, which was linked with aberrant epithelial‐mesenchymal transition, oxidative stress, mitochondrial damage and mitophagy, as well as activation of TGFβ1‐PI3K/Akt, TGFβ1‐ NOX and TGFβ1‐NLRP3 pathways." @default.
• W3147160714 created "2021-04-13" @default.
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• W3147160714 date "2021-03-29" @default.
• W3147160714 modified "2023-10-16" @default.
• W3147160714 title "Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of <scp>PM₂</scp>_.5 in mice" @default.
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• W3147160714 doi "https://doi.org/10.1002/tox.23140" @default.
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