{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:37:56Z","timestamp":1792615076661,"version":"4.5.0"},"reference-count":63,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST109\u20102320\u2010B\u2010006\u2010026\u2010MY3"],"award-info":[{"award-number":["MOST109\u20102320\u2010B\u2010006\u2010026\u2010MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST110\u20102320\u2010B\u2010006\u2010053"],"award-info":[{"award-number":["MOST110\u20102320\u2010B\u2010006\u2010053"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST111\u20102320\u2010B\u2010006\u2010015"],"award-info":[{"award-number":["MOST111\u20102320\u2010B\u2010006\u2010015"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fibrosing interstitial lung diseases (fILD) are potentially fatal with limited therapeutic options and no effective strategies to reverse fibrogenesis. Myofibroblasts are chief effector cells in fibrosis that excessively deposit collagen in the pulmonary interstitium and lead to progressive impairment of gaseous exchange.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma and lung specimens from patients with fILD were applied for detecting pentraxin 3 (PTX3) abundance by ELISA and Immunohistochemistry. Masson's trichrome and Sirius red stains and hydroxyproline assay were performed for assessing collagen accumulation in the lungs of bleomycin\u2010exposed conditional Ptx3\u2010deficient and PTX3\u2010neutralizing antibody (\u03b1PTX3i)\u2010treated mice. Downstream effectors including signaling pathways and fibrotic genes were examined for assessing CD44\u2010involved PTX3\u2010induced fibrosis in HFL1 and primary mouse fibroblasts.\n<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PTX3 was upregulated in the lungs and plasma of bleomycin\u2010exposed mice and correlated with disease severity and adverse outcomes in fILD patients. Decreased collagen accumulation, attenuation of alveolar fibrosis and fibrotic markers, and improved lung function were observed in bleomycin\u2010exposed conditional Ptx3\u2010deficient mice. PTX3 activates lung fibroblasts to differentiate towards migrative and highly collagen\u2010expressing myofibroblasts. Lung fibroblasts with CD44 inactivation attenuated the PI3K\u2010AKT1, NF\u2010\u03baB, and JNK signaling pathways and fibrotic markers. \u03b1PTX3i mimic\u2010based therapeutic studies demonstrated abrogation of the migrative fibroblast phenotype and myofibroblast activation in vitro. Notably, \u03b1PTX3i inhibited lung fibrosis, reduced collagen deposition, increased mouse survival, and improved lung function in bleomycin\u2010induced pulmonary fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study reveals new insights into the involvement of the PTX3\/CD44 axis in fibrosis and suggests PTX3 as a promising therapeutic target in fILD patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1099","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T04:14:00Z","timestamp":1667794440000},"source":"Crossref","is-referenced-by-count":26,"title":["Blockade of the pentraxin 3\/CD44 interaction attenuates lung injury\u2010induced fibrosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Jhih\u2010Ying","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University  Tainan 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