SHIH-CHAN LAIKE-MIN CHEN2026-10-162026-10-162025-12-01Pure ID: 15024957Pure UUID: 92c306a7-070d-457b-8db5-83e5e1dd7f2b10.1038/s41598-025-22711-xhttps://www.scopus.com/pages/publications/105021040677https://scholars.csmu.edu.tw/handle/123456789/30098Toxocara canis infection induces severe pulmonary pathology, including hemorrhage, inflammation, and extracellular matrix (ECM) degradation, though the underlying mechanisms remain unclear. This study explores the role of cyclooxygenase-2 (COX-2) in lung injury during T. canis infection, focusing on its regulation of plasminogen activator (PA) activity and collagen type VI (COL6) degradation. A murine model was established by orogastric inoculation of 2000 embryonated T. canis eggs. Lung tissues were analyzed via histopathology, ELISA, Western blotting, and immunohistochemistry. COX-2 inhibition with celecoxib was used to assess its effects on COX-2/PGE₂ signaling, PA activity, PI3K/AKT pathway activation, and COL6 degradation. Infection significantly upregulated COX-2, peaking at day 7, correlating with increased PA activity and COL6 cleavage (70/50 kDa fragments). Celecoxib suppressed COX-2/PGE₂, downregulated PI3K/AKT, reduced PA activity, and preserved COL6 integrity, mitigating lung injury. Mechanistically, COX-2/PGE₂ enhances PA activation via PI3K/AKT, exacerbating COL6 degradation. In conclusion, COX-2 drives lung pathology in toxocariasis by modulating PA activity and COL6 degradation, suggesting that targeting COX-2/PGE₂ signaling could ameliorate infection-induced pulmonary damage.enjournal article