{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:19:03Z","timestamp":1785525543582,"version":"3.56.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["HL130133"],"award-info":[{"award-number":["HL130133"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["HL142853"],"award-info":[{"award-number":["HL142853"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["HL130133"],"award-info":[{"award-number":["HL130133"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["HL142853"],"award-info":[{"award-number":["HL142853"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pleural conditions causing exudative effusions (empyema or complicated parapneumonia) can result in pathological pleural organization leading to pleural fibrosis (PF). Pleural mesothelial cells (PMCs) undergo mesenchymal transition (MesoMT) and acquire a profibrotic phenotype characterized by increased expression of ACTA2; collagen type I (Col-1); and phenotypic changes, including elongation, stress fiber formation, and contraction. Using RNA-sequencing analysis, we identified Tuftelin-1 (Tuft1) as a novel potential target. Although prior studies have shown that Tuft1 expression is associated with aggressive cellular phenotypes, its role in PF is unknown. Our prior studies show that inhibition of PI3K\/Akt, mTORC2, or GSK-3\u03b2 blocks MesoMT. In this study, we build on previous findings and suggest that Tuft1 plays a key role in promoting MesoMT. In human PMCs, various mediators that induce MesoMT result in upregulation of Tuft1 expression. Furthermore, we also found that Tuft1 was increased in human pleuritis tissues and in murine models of PF compared with normal lung. In our studies, TGF-\u03b2\u2013mediated increase in Tuft1 was blocked by the GSK-3\u03b2 inhibitor 9-ING-41. Knockdown of Tuft1 in vitro blocked TGF-\u03b2\u2013mediated MesoMT. Conversely, Tuft1 overexpression induced mTORC2 signaling and promoted MesoMT in the absence of TGF-\u03b2. In vivo analyses showed that mesothelial cell\u2013specific Tuft1 knockout mice (Tuft1PMC\u2212\/\u2212) were protected from Streptococcus pneumoniae\u2013mediated pleural injury. Histological analysis showed that pleural thickening and profibrotic markers were significantly reduced in Tuft1PMC\u2212\/\u2212 mice compared with wild-type control animals. These studies strongly support therapeutic targeting of Tuft1 as a novel means to mitigate PF.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0263oc","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T11:23:17Z","timestamp":1740482597000},"page":"441-450","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Tuftelin-1 in Mesomesenchymal Transition of Pleural Mesothelial Cells and the Progression of Pleural Fibrosis"],"prefix":"10.1093","volume":"73","author":[{"given":"Ann","family":"Jeffers","sequence":"first","affiliation":[{"name":"Texas Lung Injury Institute"},{"name":"Department of Cellular and Molecular Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzi","family":"Owens","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, 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