{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:42:51Z","timestamp":1792582971623,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113\u20102320\u2010B\u2010006\u2010001\u2010"],"award-info":[{"award-number":["NSTC 113\u20102320\u2010B\u2010006\u2010001\u2010"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113\u20102327\u2010B\u2010006\u2010001\u2010"],"award-info":[{"award-number":["NSTC 113\u20102327\u2010B\u2010006\u2010001\u2010"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020363","name":"Institute for Information Industry, Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC 114\u20102320\u2010B\u2010006\u2010021\u2010"],"award-info":[{"award-number":["NSTC 114\u20102320\u2010B\u2010006\u2010021\u2010"]}],"id":[{"id":"10.13039\/501100020363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020363","name":"Institute for Information Industry, Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC 114\u20102320\u2010B\u2010006\u2010041\u2010"],"award-info":[{"award-number":["NSTC 114\u20102320\u2010B\u2010006\u2010041\u2010"]}],"id":[{"id":"10.13039\/501100020363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020363","name":"Institute for Information Industry, Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC 114\u20102923\u2010B\u2010006\u2010001\u2010MY2"],"award-info":[{"award-number":["NSTC 114\u20102923\u2010B\u2010006\u2010001\u2010MY2"]}],"id":[{"id":"10.13039\/501100020363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"abstract":"<jats:p>Renal fibrosis is a hallmark of chronic kidney disease (CKD), but effective antifibrotic therapies are lacking. Pentraxin 3 (PTX3) is markedly upregulated in CKD patients and in a unilateral ureteral obstruction (UUO) model, correlating with renal injury, extracellular matrix accumulation, partial epithelial\u2013mesenchymal transition markers, and TGF\u2010\u03b21 signaling. Genetic deletion of Ptx3 significantly attenuates UUO\u2010induced fibrosis. Mechanistically, PTX3 promotes transcription of LTBP\u20101 and fibronectin, facilitating latent TGF\u2010\u03b21 activation and inducing a profibrotic partial EMT program in tubular epithelial cells without lineage conversion. Importantly, blockade of the PTX3\/CD44 axis using a neutralizing \u03b1PTX3 antibody reduced serum creatinine levels and renal fibrosis, identifying PTX3 as a promising therapeutic target for CKD.<\/jats:p>","DOI":"10.1002\/1873-3468.70480","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:06:24Z","timestamp":1792580784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutralization of the\n                    <scp>PTX3<\/scp>\n                    \/\n                    <scp>CD44<\/scp>\n                    axis suppresses\n                    <scp>TGF<\/scp>\n                    \u2010\u03b21 signaling in kidney fibrosis"],"prefix":"10.1002","author":[{"given":"Chao\u2010Chun","family":"Cheng","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen\u2010Shin","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of Surgery, National Chung Kung University Hospital, College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng\u2010Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Chieh","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology National Cheng Kung University  Tainan Taiwan"},{"name":"Department of Thoracic Surgery Chi Mei Medical Center  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh Phuong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Wei","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhih\u2010Ying","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Yin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1094-860X","authenticated-orcid":false,"given":"Ju\u2010Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University  Tainan Taiwan"},{"name":"Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology National Cheng Kung University  Tainan Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine Taipei Medical University  Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine Kaohsiung Medical University  Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1001\/jama.2019.14745","article-title":"Chronic kidney disease diagnosis and management: a review","volume":"322","author":"Chen TK","year":"2019","journal-title":"JAMA"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s10157-013-0781-0","article-title":"Role of the endothelial\u2010to\u2010mesenchymal transition in renal fibrosis of chronic kidney disease","volume":"17","author":"He JH","year":"2013","journal-title":"Clin Exp Nephrol"},{"issue":"1","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1755-1536-5-S1-S5","article-title":"The myofibroblast, multiple origins for major roles in normal and pathological tissue repair","volume":"5","author":"Micallef L","year":"2012","journal-title":"Fibrogenesis Tissue Repair"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/ki.2011.77","article-title":"Scar wars: mapping the fate of epithelial\u2010mesenchymal\u2010myofibroblast transition","volume":"80","author":"Quaggin SE","year":"2011","journal-title":"Kidney Int"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrneph.2015.133","article-title":"Fibrosis: targeting EMT to reverse renal fibrosis","volume":"11","author":"Allison SJ","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2020.569322","article-title":"New insights into the role and mechanism of partial epithelial\u2010mesenchymal transition in kidney fibrosis","volume":"11","author":"Sheng LL","year":"2020","journal-title":"Front Physiol"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: from mechanisms to therapeutic medicines","volume":"8","author":"Huang R","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrneph.2016.54","article-title":"Developmental signalling pathways in renal fibrosis: the roles of notch, Wnt and hedgehog","volume":"12","author":"Edeling M","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm5070063","article-title":"Mechanisms of TGFbeta\u2010induced epithelial\u2010mesenchymal transition","volume":"5","author":"Moustakas A","year":"2016","journal-title":"J Clin Med"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/path.5680","article-title":"TGF\u2010\u03b2 as a driver of fibrosis: physiological roles and therapeutic opportunities","volume":"254","author":"Budi EH","year":"2021","journal-title":"J Pathol"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"18758","DOI":"10.1073\/pnas.0805411105","article-title":"Perturbation of transforming growth factor (TGF)\u2010beta1 association with latent TGF\u2010beta binding protein yields inflammation and tumors","volume":"105","author":"Yoshinaga K","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1083\/jcb.200312172","article-title":"Integrin \u03b1\u03b2\u2010mediated activation of latent TGF\u2010\u03b2 requires the latent TGF\u2010\u03b2 binding protein\u20101","volume":"165","author":"Annes JP","year":"2004","journal-title":"J Cell Biol"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1096\/fj.05-4134com","article-title":"Fibronectin is required for integrin \u03b1v\u03b26\u2010mediated activation of latent TGF\u2010\u03b2 complexes containing LTBP\u20101","volume":"19","author":"Fontana L","year":"2005","journal-title":"FASEB J"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"18871","DOI":"10.1074\/jbc.M410762200","article-title":"Fibronectin regulates latent transforming growth factor\u2010beta (TGF beta) by controlling matrix assembly of latent TGF beta\u2010binding protein\u20101","volume":"280","author":"Dallas SL","year":"2005","journal-title":"J Biol Chem"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.18632\/aging.204070","article-title":"Pentraxin 3 depletion (PTX3 KD) inhibited myocardial fibrosis in heart failure after myocardial infarction","volume":"14","author":"Xu Y","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"422.e11","DOI":"10.1016\/j.neurobiolaging.2010.09.017","article-title":"CCAAT\/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage\u2010mediated phagocytosis of dying neuron cells","volume":"33","author":"Ko CY","year":"2012","journal-title":"Neurobiol Aging"},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2023.166807","article-title":"Pentraxin 3 plays a key role in tubular cell senescence and renal fibrosis through inducing \u00df\u2010catenin signaling","volume":"1869","author":"Luo P","year":"2023","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.2215\/CJN.00870207","article-title":"Plasma pentraxin 3 in patients with chronic kidney disease: associations with renal function, protein\u2010energy wasting, cardiovascular disease, and mortality","volume":"2","author":"Tong M","year":"2007","journal-title":"Clin J Am Soc Nephrol"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1159\/000453159","article-title":"Pentraxin 3 activates JNK signaling and regulates the epithelial\u2010to\u2010mesenchymal transition in renal fibrosis","volume":"40","author":"Hung TW","year":"2016","journal-title":"Cell Physiol Biochem"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"e724","DOI":"10.1002\/ctm2.724","article-title":"Disruption of the pentraxin 3\/CD44 interaction as an efficient therapy for triple\u2010negative breast cancers","volume":"12","author":"Hsiao YW","year":"2022","journal-title":"Clin Transl Med"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"23987","DOI":"10.18632\/oncotarget.4364","article-title":"Targeting chemotherapy\u2010induced PTX3 in tumor stroma to prevent the progression of drug\u2010resistant cancers","volume":"6","author":"Chi JY","year":"2015","journal-title":"Oncotarget"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.1099","article-title":"Blockade of the pentraxin 3\/CD44 interaction attenuates lung injury\u2010induced fibrosis","volume":"12","author":"Chi Y","year":"2022","journal-title":"Clin Transl Med"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"113962","DOI":"10.1016\/j.biopha.2022.113962","article-title":"Pentraxin 3 regulates tyrosine kinase inhibitor\u2010associated cardiomyocyte contraction and mitochondrial dysfunction via ERK\/JNK signalling pathways","volume":"157","author":"Chen YT","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12929-023-00991-7","article-title":"Inactivation of pentraxin 3 suppresses M2\u2010like macrophage activity and immunosuppression in colon cancer","volume":"31","author":"Chen FW","year":"2024","journal-title":"J Biomed Sci"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1083\/jcb.201402006","article-title":"Prestress in the extracellular matrix sensitizes latent TGF\u2010beta1 for activation","volume":"207","author":"Klingberg F","year":"2014","journal-title":"J Cell Biol"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.matbio.2015.05.005","article-title":"Latent TGF\u2010beta\u2010binding proteins","volume":"47","author":"Robertson IB","year":"2015","journal-title":"Matrix Biol"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"116231","DOI":"10.1016\/j.bone.2021.116231","article-title":"PTX3 promotes osteogenic differentiation by triggering HA\/CD44\/FAK\/AKT positive feedback loop in an inflammatory environment","volume":"154","author":"Dong W","year":"2022","journal-title":"Bone"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s12079-013-0216-4","article-title":"TGF\u2010beta1 induces EMT reprogramming of porcine bladder urothelial cells into collagen producing fibroblasts\u2010like cells in a Smad2\/Smad3\u2010dependent manner","volume":"8","author":"Islam SS","year":"2014","journal-title":"J Cell Commun Signal"},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1016\/j.bbagen.2014.02.004","article-title":"TGFbeta and matrix\u2010regulated epithelial to mesenchymal transition","volume":"1840","author":"Moustakas A","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"e_1_2_9_31_1","first-page":"136","article-title":"TGF\u2010beta in developmental and fibrogenic EMTs","volume":"86","author":"Lee JH","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/3295725","article-title":"Long pentraxin 3 as a broader biomarker for multiple risk factors in end\u2010stage renal disease: association with all\u2010cause mortality","volume":"2019","author":"Valente MJ","year":"2019","journal-title":"Mediat Inflamm"},{"key":"e_1_2_9_33_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.xkme.2024.100800","article-title":"Pentraxin\u20103 and outcomes in CKD: a systematic review and meta\u2010analysis","volume":"6","author":"Li L","year":"2024","journal-title":"Kidney Medicine"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2023.154901","article-title":"PTX3 shapes profibrotic immune cells and epithelial\/fibroblast repair and regeneration in a murine model of pulmonary fibrosis","volume":"251","author":"d'Amati A","year":"2023","journal-title":"Pathol Res Pract"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/08977194.2011.595714","article-title":"TGF\u2010beta signaling in fibrosis","volume":"29","author":"Biernacka A","year":"2011","journal-title":"Growth Factors"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1113\/JP274492","article-title":"Transforming growth factor\u2010beta signalling in renal fibrosis: from Smads to non\u2010coding RNAs","volume":"596","author":"Tang PM","year":"2018","journal-title":"J Physiol"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fcell.2020.00123","article-title":"Diverse role of TGF\u2010beta in kidney disease","volume":"8","author":"Gu YY","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.matbio.2015.05.006","article-title":"The extracellular matrix and transforming growth factor\u2010beta1: tale of a strained relationship","volume":"47","author":"Hinz B","year":"2015","journal-title":"Matrix Biol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.apsb.2022.01.007","article-title":"Multifunctional regulatory protein connective tissue growth factor (CTGF): a potential therapeutic target for diverse diseases","volume":"12","author":"Fu M","year":"2022","journal-title":"Acta Pharm Sin B"}],"container-title":["FEBS Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.70480","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1873-3468.70480","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.70480","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:06:29Z","timestamp":1792580789000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1873-3468.70480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":38,"alternative-id":["10.1002\/1873-3468.70480"],"URL":"https:\/\/doi.org\/10.1002\/1873-3468.70480","archive":["Portico"],"relation":{},"ISSN":["0014-5793","1873-3468"],"issn-type":[{"value":"0014-5793","type":"print"},{"value":"1873-3468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"assertion":[{"value":"2026-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1873-3468.70480"}}