{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:15:00Z","timestamp":1770801300458,"version":"3.50.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells (PMCs) may contribute to PF through acquisition of a profibrotic phenotype, mesothelial\u2013mesenchymal transition (MesoMT), which is characterized by increased expression of \u03b1-SMA (\u03b1-smooth muscle actin) and other myofibroblast markers. Although MesoMT has been implicated in the pathogenesis of PF, the role of the reactive oxygen species and the NOX (nicotinamide adenine dinucleotide phosphate oxidase) family in pleural remodeling remains unclear. Here, we show that NOX1 expression is enhanced in nonspecific human pleuritis and is induced in PMCs by THB (thrombin). 4-Hydroxy-2-nonenal, an indicator of reactive oxygen species damage, was likewise increased in our mouse model of pleural injury. NOX1 downregulation blocked THB- and Xa (factor Xa)\u2013mediated MesoMT, as did pharmacologic inhibition of NOX1 with ML-171. NOX1 inhibition also reduced phosphorylation of Akt, p65, and tyrosine 216\u2013GSK-3\u03b2, signaling molecules previously shown to be implicated in MesoMT. Conversely, ML-171 did not reverse established MesoMT. NOX4 downregulation attenuated TGF-\u03b2\u2013 and THB-mediated MesoMT. However, NOX1 downregulation did not affect NOX4 expression. NOX1- and NOX4-deficient mice were also protected in our mouse model of Streptococcus pneumoniae\u2013mediated PF. These data show that NOX1 and NOX4 are critical determinants of MesoMT.<\/jats:p>","DOI":"10.1165\/rcmb.2020-0077oc","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T19:34:03Z","timestamp":1611948843000},"page":"492-503","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":10,"title":["NOX1 Promotes Mesothelial\u2013Mesenchymal Transition Through Modulation of Reactive Oxygen Species\u2013Mediated Signaling"],"prefix":"10.1093","volume":"64","author":[{"given":"Wenyi","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Jeffers","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, 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