{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:59:46Z","timestamp":1781877586346,"version":"3.54.5"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":114,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91949110"],"award-info":[{"award-number":["91949110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    . Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial\u2010mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT during pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)\/soluble epoxide hydrolase (sEH) and cyclooxygenase\u20102 (COX\u20102) metabolic disorders of ARA in EMT during PF.\n                    <jats:italic>Methods<\/jats:italic>\n                    . A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL\/6\u2009J mice. A COX\u20102\/sEH dual inhibitor PTUPB was used to establish the function of CYPs\/COX\u20102 dysregulation to EMT in PF mice.\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments, murine alveolar epithelial cells (MLE12) and human alveolar epithelial cells (A549) were used to explore the roles and mechanisms of PTUPB on transforming growth factor (TGF)\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1\u2010induced EMT.\n                    <jats:italic>Results<\/jats:italic>\n                    . PTUPB treatment reversed the increase of mesenchymal marker molecule\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010smooth muscle actin (\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010SMA) and the loss of epithelial marker molecule E\u2010cadherin in lung tissue of PF mice.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , COX\u20102 and sEH protein levels were increased in TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1\u2010treated alveolar epithelial cells (AECs). PTUPB decreased the expression of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010SMA and restored the expression of E\u2010cadherin in TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1\u2010treated AECs, accompanied by reduced migration and collagen synthesis. Moreover, PTUPB attenuated TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1\u2010Smad2\/3 pathway activation in AECs\n                    <jats:italic>via<\/jats:italic>\n                    Nrf2 antioxidant cascade.\n                    <jats:italic>Conclusion<\/jats:italic>\n                    . PTUPB inhibits EMT in AECs\n                    <jats:italic>via<\/jats:italic>\n                    Nrf2\u2010mediated inhibition of the TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1\u2010Smad2\/3 pathway, which holds great promise for the clinical treatment of PF.\n                  <\/jats:p>","DOI":"10.1155\/2022\/5759626","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T19:20:09Z","timestamp":1650914409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["COX\u20102\/sEH Dual Inhibitor PTUPB Attenuates Epithelial\u2010Mesenchymal Transformation of Alveolar Epithelial Cells\n                    <i>via<\/i>\n                    Nrf2\u2010Mediated Inhibition of TGF\u2010\n                    <i>\u03b2<\/i>\n                    1\/Smad 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