{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:58:44Z","timestamp":1790420324095,"version":"4.1.0"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission Research Executive Agency","award":["669026"],"award-info":[{"award-number":["669026"]}]},{"name":"European Commission Research Executive Agency","award":["669026"],"award-info":[{"award-number":["669026"]}]},{"DOI":"10.13039\/501100003447","name":"State Scholarships Foundation","doi-asserted-by":"publisher","award":["MIS 5000432"],"award-info":[{"award-number":["MIS 5000432"]}],"id":[{"id":"10.13039\/501100003447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Fibrotic diseases cover a spectrum of systemic and organ-specific maladies that affect a large portion of the population, currently without cure. The shared characteristic these diseases feature is their uncontrollable fibrogenesis deemed responsible for the accumulated damage in the susceptible tissues.<jats:italic>Idiopathic Pulmonary Fibrosis<\/jats:italic>, an interstitial lung disease, is one of the most common and studied fibrotic diseases and still remains an active research target. In this study we highlight unique and common (i) genes, (ii) biological pathways and (iii) candidate repurposed drugs among 9 fibrotic diseases. We identify 7 biological pathways involved in all 9 fibrotic diseases as well as pathways unique to some of these diseases. Based on our Drug Repurposing results, we suggest captopril and ibuprofen that both appear to slow the progression of fibrotic diseases according to existing bibliography. We also recommend nafcillin and memantine, which haven\u2019t been studied against fibrosis yet, for further wet-lab experimentation. We also observe a group of cardiomyopathy-related pathways that are exclusively highlighted for<jats:italic>Oral Submucous Fibrosis<\/jats:italic>. We suggest digoxin to be tested against<jats:italic>Oral Submucous Fibrosis<\/jats:italic>, since we observe cardiomyopathy-related pathways implicated in<jats:italic>Oral Submucous Fibrosis<\/jats:italic>and there is bibliographic evidence that digoxin may potentially clear myocardial fibrosis. Finally, we establish that<jats:italic>Idiopathic Pulmonary Fibrosis<\/jats:italic>shares several involved genes, biological pathways and candidate inhibiting-drugs with<jats:italic>Dupuytren\u2019s Disease<\/jats:italic>,<jats:italic>IgG4-related Disease<\/jats:italic>,<jats:italic>Systemic Sclerosis<\/jats:italic>and<jats:italic>Cystic Fibrosis<\/jats:italic>. We propose that treatments for these fibrotic diseases should be jointly pursued.<\/jats:p>","DOI":"10.1371\/journal.pone.0249687","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T18:44:14Z","timestamp":1617821054000},"page":"e0249687","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fibrotic expression profile analysis reveals repurposed drugs with potential anti-fibrotic mode of action"],"prefix":"10.1371","volume":"16","author":[{"given":"Evangelos","family":"Karatzas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-679X","authenticated-orcid":true,"given":"Andrea C.","family":"Kakouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kolios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Delis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-3363","authenticated-orcid":true,"given":"George M.","family":"Spyrou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"issue":"3","key":"pone.0249687.ref001","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1172\/JCI31487","article-title":"Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases","volume":"117","author":"TA Wynn","year":"2007","journal-title":"The Journal of clinical investigation"},{"issue":"18","key":"pone.0249687.ref002","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1073\/pnas.1621375114","article-title":"Unifying mechanism for different fibrotic diseases","volume":"114","author":"G Wernig","year":"2017","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pone.0249687.ref003","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1172\/JCI93557","article-title":"Extracellular matrix as a driver of progressive fibrosis","volume":"128","author":"J Herrera","year":"2018","journal-title":"The Journal of clinical investigation"},{"key":"pone.0249687.ref004","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"AD Theocharis","year":"2016","journal-title":"Advanced drug delivery reviews"},{"issue":"22","key":"pone.0249687.ref005","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.3748\/wjg.v13.i22.3056","article-title":"Transforming growth factor-\u03b2 and fibrosis.","volume":"13","author":"F Verrecchia","year":"2007","journal-title":"World journal of gastroenterology: WJG."},{"key":"pone.0249687.ref006","first-page":"1","volume-title":"Human fibrotic diseases: current challenges in fibrosis research","author":"J Rosenbloom","year":"2017"},{"issue":"4","key":"pone.0249687.ref007","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cytogfr.2004.03.006","article-title":"Regulation of PDGF and its receptors in fibrotic diseases","volume":"15","author":"JC Bonner","year":"2004","journal-title":"Cytokine & growth factor reviews"},{"issue":"3","key":"pone.0249687.ref008","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1183\/09031936.00185114","article-title":"Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review","volume":"46","author":"J Hutchinson","year":"2015","journal-title":"European Respiratory Journal"},{"issue":"5","key":"pone.0249687.ref009","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"Diagnosis of idiopathic pulmonary fibrosis. An official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"198","author":"G Raghu","year":"2018","journal-title":"American journal of respiratory and critical care medicine"},{"key":"pone.0249687.ref010","doi-asserted-by":"crossref","unstructured":"Karatzas E, Delis A, Kolios G, Spyrou G, editors. Exploring Fibrotic Disease Networks to Identify Common Molecular Mechanisms with IPF. 2019 IEEE 19th International Conference on Bioinformatics and Bioengineering (BIBE); 2019: IEEE.","DOI":"10.1109\/BIBE.2019.00022"},{"key":"pone.0249687.ref011","article-title":"PathWalks: Identifying pathway communities using a disease-related map of integrated information","author":"E Karatzas","year":"2020","journal-title":"Bioinformatics (Oxford, England)."},{"issue":"96","key":"pone.0249687.ref012","doi-asserted-by":"crossref","first-page":"96ps35","DOI":"10.1126\/scitranslmed.3001512","article-title":"The emergence of genome-based drug repositioning","volume":"3","author":"YA Lussier","year":"2011","journal-title":"Science translational medicine"},{"key":"pone.0249687.ref013","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.csbj.2019.05.010","article-title":"A Web Tool for Ranking Candidate Drugs Against a Selected Disease Based on a Combination of Functional and Structural Criteria.","volume":"17","author":"E Karatzas","year":"2019","journal-title":"Computational and structural biotechnology journal"},{"issue":"5886","key":"pone.0249687.ref014","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.1158140","article-title":"Drug target identification using side-effect similarity","volume":"321","author":"M Campillos","year":"2008","journal-title":"Science (New York, NY)."},{"issue":"1","key":"pone.0249687.ref015","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"R Edgar","year":"2002","journal-title":"Nucleic acids research"},{"issue":"7","key":"pone.0249687.ref016","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic acids research"},{"issue":"1","key":"pone.0249687.ref017","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"pone.0249687.ref018","first-page":"5","article-title":"From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline.","author":"Y Chen","year":"2016","journal-title":"F1000Research"},{"key":"pone.0249687.ref019","article-title":"PathWalks: Identifying pathway communities using a disease-related map of integrated information.","author":"E Karatzas","year":"2020","journal-title":"BioRxiv."},{"issue":"11","key":"pone.0249687.ref020","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome research"},{"issue":"22","key":"pone.0249687.ref021","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1093\/bioinformatics\/btq562","article-title":"GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop","volume":"26","author":"J Montojo","year":"2010","journal-title":"Bioinformatics"},{"issue":"D1","key":"pone.0249687.ref022","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: new perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"M Kanehisa","year":"2017","journal-title":"Nucleic acids research"},{"issue":"1","key":"pone.0249687.ref023","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/gb-2008-9-s1-s4","article-title":"GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function","volume":"9","author":"S Mostafavi","year":"2008","journal-title":"Genome biology"},{"issue":"suppl_2","key":"pone.0249687.ref024","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gkq537","article-title":"The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function","volume":"38","author":"D Warde-Farley","year":"2010","journal-title":"Nucleic acids research"},{"issue":"W1","key":"pone.0249687.ref025","doi-asserted-by":"crossref","first-page":"W115","DOI":"10.1093\/nar\/gkt533","article-title":"GeneMANIA prediction server 2013 update","volume":"41","author":"K Zuberi","year":"2013","journal-title":"Nucleic acids research"},{"issue":"302","key":"pone.0249687.ref026","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/14786440009463897","article-title":"On the criterion that a given system of deviations from the probable in the case of a correlated system of variables is such that it can be reasonably supposed to have arisen from random sampling.","volume":"50","author":"K. X Pearson","year":"1900","journal-title":"The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science."},{"issue":"1","key":"pone.0249687.ref027","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Y Benjamini","year":"1995","journal-title":"Journal of the Royal statistical society: series B (Methodological)."},{"issue":"6","key":"pone.0249687.ref028","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","article-title":"A next generation connectivity map: L1000 platform and the first 1,000,000 profiles","volume":"171","author":"A Subramanian","year":"2017","journal-title":"Cell"},{"key":"pone.0249687.ref029","doi-asserted-by":"crossref","first-page":"16015","DOI":"10.1038\/npjsba.2016.15","article-title":"L1000CDS 2: LINCS L1000 characteristic direction signatures search engine","volume":"2","author":"Q Duan","year":"2016","journal-title":"NPJ systems biology and applications"},{"issue":"1\u20133","key":"pone.0249687.ref030","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"CA Lipinski","year":"1997","journal-title":"Advanced drug delivery reviews"},{"issue":"12","key":"pone.0249687.ref031","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"DF Veber","year":"2002","journal-title":"Journal of medicinal chemistry"},{"issue":"17","key":"pone.0249687.ref032","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1093\/bioinformatics\/btr406","article-title":"APCluster: an R package for affinity propagation clustering","volume":"27","author":"U Bodenhofer","year":"2011","journal-title":"Bioinformatics"},{"key":"pone.0249687.ref033","doi-asserted-by":"crossref","first-page":"170029","DOI":"10.1038\/sdata.2017.29","article-title":"A standard database for drug repositioning.","volume":"4","author":"AS Brown","year":"2017","journal-title":"Scientific data"},{"key":"pone.0249687.ref034","article-title":"ChemBioServer 2.0: An advanced web server for filtering, clustering and networking of chemical compounds facilitating both drug discovery and repurposing","author":"E Karatzas","year":"2020","journal-title":"Bioinformatics (Oxford, England)."},{"issue":"D1","key":"pone.0249687.ref035","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database for 2018","volume":"46","author":"DS Wishart","year":"2018","journal-title":"Nucleic acids research"},{"issue":"D1","key":"pone.0249687.ref036","doi-asserted-by":"crossref","first-page":"D963","DOI":"10.1093\/nar\/gky963","article-title":"DrugCentral 2018: an update","volume":"47","author":"O Ursu","year":"2019","journal-title":"Nucleic acids research"},{"issue":"D1","key":"pone.0249687.ref037","doi-asserted-by":"crossref","first-page":"D1068","DOI":"10.1093\/nar\/gkx1143","article-title":"DGIdb 3.0: a redesign and expansion of the drug\u2013gene interaction database","volume":"46","author":"KC Cotto","year":"2018","journal-title":"Nucleic acids research"},{"issue":"14","key":"pone.0249687.ref038","doi-asserted-by":"crossref","first-page":"10425","DOI":"10.1016\/S0021-9258(18)82217-7","article-title":"Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase","volume":"268","author":"L Kjeldsen","year":"1993","journal-title":"Journal of Biological Chemistry"},{"issue":"7019","key":"pone.0249687.ref039","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nature03104","article-title":"Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron","volume":"432","author":"TH Flo","year":"2004","journal-title":"Nature"},{"issue":"3","key":"pone.0249687.ref040","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/bjd.13779","article-title":"A possible contribution of lipocalin\u20102 to the development of dermal fibrosis, pulmonary vascular involvement and renal dysfunction in systemic sclerosis","volume":"173","author":"T Takahashi","year":"2015","journal-title":"British Journal of Dermatology"},{"issue":"8","key":"pone.0249687.ref041","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136994","article-title":"Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease","volume":"10","author":"S Nakagawa","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0249687.ref042","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1620\/tjem.222.319","article-title":"Increased urinary lipocalin-2 reflects matrix metalloproteinase-9 activity in chronic hepatitis C with hepatic fibrosis","volume":"222","author":"J-W Kim","year":"2010","journal-title":"The Tohoku journal of experimental medicine"},{"issue":"6","key":"pone.0249687.ref043","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1002\/hep.22896","article-title":"Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease","volume":"49","author":"KL Milner","year":"2009","journal-title":"Hepatology"},{"issue":"5","key":"pone.0249687.ref044","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/j.1478-3231.2011.02495.x","article-title":"Induction of lipocalin\u20102 expression in acute and chronic experimental liver injury moderated by pro\u2010inflammatory cytokines interleukin\u20101\u03b2 through nuclear factor\u2010\u03baB activation.","volume":"31","author":"E Borkham\u2010Kamphorst","year":"2011","journal-title":"Liver International."},{"issue":"6","key":"pone.0249687.ref045","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1083\/jcb.111.6.3155","article-title":"Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure","volume":"111","author":"WS Argraves","year":"1990","journal-title":"The Journal of cell biology"},{"issue":"6","key":"pone.0249687.ref046","article-title":"Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-\u03b21 in airway smooth muscle cells.","volume":"8","author":"L Chen","year":"2013","journal-title":"PLoS one."},{"issue":"9","key":"pone.0249687.ref047","article-title":"Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases.","volume":"1","author":"G Liu","year":"2016","journal-title":"JCI insight."},{"key":"pone.0249687.ref048","doi-asserted-by":"crossref","first-page":"9496","DOI":"10.1038\/srep09496","article-title":"Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts","volume":"5","author":"Q Ge","year":"2015","journal-title":"Scientific reports"},{"key":"pone.0249687.ref049","first-page":"A5173","volume-title":"The Serum Level Of Fibulin-1 Is Elevated In Idiopathic Pulmonary Fibrosis. C103 PATHOGENESIS, BIOMARKERS, AND RISK FACTORS FOR INTERSTITIAL LUNG DISEASE: FROM BENCH TO BEDSIDE","author":"J Jaffar","year":"2012"},{"issue":"3","key":"pone.0249687.ref050","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000354217","article-title":"Aortic valve stenosis and atrial fibrillation influence plasma fibulin-1 levels in patients treated with coronary bypass surgery","volume":"126","author":"ML Hansen","year":"2013","journal-title":"Cardiology"},{"issue":"12","key":"pone.0249687.ref051","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1109\/TVCG.2014.2346248","article-title":"UpSet: visualization of intersecting sets","volume":"20","author":"A Lex","year":"2014","journal-title":"IEEE transactions on visualization and computer graphics"},{"key":"pone.0249687.ref052","article-title":"Arena3Dweb: Interactive 3D visualization of multilayered networks.","author":"E Karatzas","year":"2020","journal-title":"bioRxiv."},{"issue":"7","key":"pone.0249687.ref053","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.joms.2008.12.056","article-title":"Drug treatment of oral submucous fibrosis: a review of the literature","volume":"67","author":"X Jiang","year":"2009","journal-title":"Journal of oral and maxillofacial surgery"},{"issue":"4","key":"pone.0249687.ref054","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/0970-9290.29865","article-title":"Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis","volume":"17","author":"R Rajendran","year":"2006","journal-title":"Indian Journal of dental research"},{"issue":"9","key":"pone.0249687.ref055","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1600-0714.1995.tb01209.x","article-title":"Clinical evaluation of different treatment methods for oral submucous fibrosis. A 10\u2010year experience with 150 cases","volume":"24","author":"D Lai","year":"1995","journal-title":"Journal of oral pathology & medicine"},{"issue":"6","key":"pone.0249687.ref056","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0901-5027(87)80055-3","article-title":"Clinical experience with the use of peripheral vasodilator in oral disorders","volume":"16","author":"J Sharma","year":"1987","journal-title":"International journal of oral and maxillofacial surgery"},{"issue":"1","key":"pone.0249687.ref057","first-page":"50","article-title":"Clinical treatment observation of tea pigment for oral submucous fibrosis","volume":"16","author":"X Li","year":"1998","journal-title":"Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology"},{"issue":"4","key":"pone.0249687.ref058","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1177\/000348945706600420","article-title":"LXXXVII Submucous Fibrosis of the Palate and Cheek.","volume":"66","author":"JV DeSa","year":"1957","journal-title":"Annals of Otology, Rhinology & Laryngology."},{"issue":"5","key":"pone.0249687.ref059","first-page":"665","article-title":"Efficacy of hydrocortisone acetate\/hyaluronidase vs triamcinolone acetonide\/hyaluronidase in the treatment of oral submucous fibrosis","volume":"131","author":"M Singh","year":"2010","journal-title":"Indian Journal of Medical Research"},{"issue":"2","key":"pone.0249687.ref060","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jep.2007.03.011","article-title":"Effects of curcumin in treatment of experimental pulmonary fibrosis: a comparison with hydrocortisone","volume":"112","author":"M Xu","year":"2007","journal-title":"Journal of ethnopharmacology"},{"issue":"1","key":"pone.0249687.ref061","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/(SICI)1099-0496(199707)24:1<48::AID-PPUL8>3.0.CO;2-F","article-title":"Lower respiratory illness in infants and young children with cystic fibrosis.","volume":"24","author":"RS Tepper","year":"1997","journal-title":"Pediatric pulmonology."},{"issue":"1\u20134","key":"pone.0249687.ref062","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3109\/rhe1.1957.3.issue-1-4.11","article-title":"Hydrocortisone Acetate in the Local Treatment of Fibroses.","volume":"3","author":"L Zachari\u00e6","year":"1957","journal-title":"Acta Rheumatologica Scandinavica."},{"issue":"21","key":"pone.0249687.ref063","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.2169\/internalmedicine.45.1759","article-title":"IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement","volume":"45","author":"T Tanabe","year":"2006","journal-title":"Internal medicine"},{"issue":"1","key":"pone.0249687.ref064","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1751-1097.1999.tb05304.x","article-title":"Alterations of hairless mouse skin exposed to chronic UV irradiation and its prevention by hydrocortisone","volume":"69","author":"H Mitani","year":"1999","journal-title":"Photochemistry and photobiology"},{"key":"pone.0249687.ref065","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.biopha.2018.09.153","article-title":"Memantine, an NMDA receptor antagonist, attenuates cardiac remodeling, lipid peroxidation and neutrophil recruitment in heart failure: A cardioprotective agent?","volume":"108","author":"S Abbaszadeh","year":"2018","journal-title":"Biomedicine & Pharmacotherapy."},{"issue":"5","key":"pone.0249687.ref066","article-title":"NMDA receptor antagonist attenuates bleomycin-induced acute lung injury","volume":"10","author":"Y Li","year":"2015","journal-title":"PLoS One"},{"issue":"D1","key":"pone.0249687.ref067","doi-asserted-by":"crossref","first-page":"D1202","DOI":"10.1093\/nar\/gkv951","article-title":"PubChem substance and compound databases","volume":"44","author":"S Kim","year":"2016","journal-title":"Nucleic acids research"},{"issue":"1","key":"pone.0249687.ref068","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13321-015-0069-3","article-title":"Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations?","volume":"7","author":"D Bajusz","year":"2015","journal-title":"Journal of cheminformatics"},{"issue":"12","key":"pone.0249687.ref069","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1021\/ac60362a002","article-title":"Similarity measures for the classification of binary infrared data","volume":"47","author":"H Woodruff","year":"1975","journal-title":"Analytical Chemistry"},{"issue":"11","key":"pone.0249687.ref070","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1136\/gut.2008.157420","article-title":"Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats","volume":"58","author":"Y-H Paik","year":"2009","journal-title":"Gut"},{"issue":"7","key":"pone.0249687.ref071","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1478-3231.2010.02256.x","article-title":"Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat","volume":"30","author":"E Ch\u00e1vez","year":"2010","journal-title":"Liver International"},{"issue":"3","key":"pone.0249687.ref072","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00580-012-1427-4","article-title":"Antifibrotic potential of a selective COX-2 inhibitor (celecoxib) on liver fibrosis in rats.","volume":"22","author":"MM Ftahy","year":"2013","journal-title":"Comparative Clinical Pathology"},{"issue":"7","key":"pone.0249687.ref073","article-title":"Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis","volume":"8","author":"J-H Gao","year":"2013","journal-title":"PloS one"},{"issue":"11","key":"pone.0249687.ref074","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1111\/jgh.12641","article-title":"Celecoxib attenuates hepatic cirrhosis through inhibition of epithelial\u2010to\u2010mesenchymal transition of hepatocytes","volume":"29","author":"SL Wen","year":"2014","journal-title":"Journal of gastroenterology and hepatology"},{"issue":"1","key":"pone.0249687.ref075","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1478-3231.2005.01202.x","article-title":"Effect of celecoxib on experimental liver fibrosis in rat","volume":"26","author":"AY Hui","year":"2006","journal-title":"Liver International"},{"issue":"3\u20134","key":"pone.0249687.ref076","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.prostaglandins.2008.10.002","article-title":"Celecoxib exacerbates hepatic fibrosis and induces hepatocellular necrosis in rats treated with porcine serum","volume":"88","author":"H Liu","year":"2009","journal-title":"Prostaglandins & other lipid mediators"},{"issue":"1","key":"pone.0249687.ref077","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1478-3231.2008.01760.x","article-title":"The anti\u2010inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct\u2010ligated rats","volume":"29","author":"J Yu","year":"2009","journal-title":"Liver International"},{"issue":"2","key":"pone.0249687.ref078","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1124\/mol.118.111831","article-title":"Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon Tetrachloride\u2013Induced Model of Liver Injury","volume":"94","author":"TR Harris","year":"2018","journal-title":"Molecular pharmacology"},{"issue":"1","key":"pone.0249687.ref079","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/jcmm.12709","article-title":"Celecoxib prevents pressure overload\u2010induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress","volume":"20","author":"C Zhang","year":"2016","journal-title":"Journal of cellular and molecular medicine"},{"issue":"10","key":"pone.0249687.ref080","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1007\/s00228-007-0346-9","article-title":"Digoxin and mortality in atrial fibrillation: a prospective cohort study","volume":"63","author":"P Hallberg","year":"2007","journal-title":"European journal of clinical pharmacology"},{"issue":"3","key":"pone.0249687.ref081","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/cs0890277","article-title":"Effect of oral digoxin, topical ouabain and salbutamol on transepithelial nasal potential difference in patients with cystic fibrosis","volume":"89","author":"D Peckham","year":"1995","journal-title":"Clinical Science"},{"issue":"6","key":"pone.0249687.ref082","first-page":"471","article-title":"Cystic fibrosis complicated by heart failure","volume":"122","author":"AJ Moss","year":"1975","journal-title":"Western Journal of Medicine"},{"issue":"5","key":"pone.0249687.ref083","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1378\/chest.82.5.543","article-title":"The effect of digoxin on exercise capacity and exercising cardiac function in cystic fibrosis.","volume":"82","author":"AL Coates","year":"1982","journal-title":"Chest"},{"issue":"6","key":"pone.0249687.ref084","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/ajh.2012.17","article-title":"Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure","volume":"25","author":"ST Haller","year":"2012","journal-title":"American journal of hypertension"},{"issue":"4","key":"pone.0249687.ref085","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1056\/NEJM198201283060405","article-title":"Captopril.","volume":"306","author":"DG Vidt","year":"1982","journal-title":"New England Journal of Medicine"},{"issue":"4","key":"pone.0249687.ref086","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/jat.1212","article-title":"Antifibrotic effect of captopril and enalapril on paraquat\u2010induced lung fibrosis in rats.","volume":"27","author":"M Ghazi\u2010Khansari","year":"2007","journal-title":"Journal of Applied Toxicology: An International Journal."},{"issue":"13","key":"pone.0249687.ref087","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2174\/138161207780618803","article-title":"Effects on cytokines and histology by treatment with the ACE inhibitor captopril and the antioxidant retinoic acid in the monocrotaline model of experimentally induced lung fibrosis","volume":"13","author":"RC Baybutt","year":"2007","journal-title":"Current pharmaceutical design"},{"issue":"1_Pt_1","key":"pone.0249687.ref088","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/ajh\/4.1.51","article-title":"Coronary Vascular Remodeling and Myocardial Fibrosis in the Rat with Renovascular Hypertension Response to Captopril","volume":"4","author":"JE Jalil","year":"1991","journal-title":"American journal of hypertension"},{"issue":"3","key":"pone.0249687.ref089","first-page":"349","article-title":"Captopril preserves function and ultrastructure in experimental radiation nephropathy","volume":"75","author":"EP Cohen","year":"1996","journal-title":"Laboratory investigation; a journal of technical methods and pathology"},{"issue":"9","key":"pone.0249687.ref090","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1440-1827.1994.tb02944.x","article-title":"Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum\u2010induced rat liver fibrosis","volume":"44","author":"SG Ramos","year":"1994","journal-title":"Pathology international"},{"issue":"5","key":"pone.0249687.ref091","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1097\/00054725-200409000-00007","article-title":"Prevention of fibrosis in experimental colitis by captopril: the role of TGF-\u03b21.","volume":"10","author":"D Wengrower","year":"2004","journal-title":"Inflammatory bowel diseases."},{"issue":"2\u20133","key":"pone.0249687.ref092","first-page":"159","article-title":"Anti-fibrogenic effects of captopril and candesartan cilexetil on the hepatic fibrosis development in rat: the effect of AT1-R blocker on the hepatic fibrosis.","volume":"55","author":"I Tuncer","year":"2003","journal-title":"Experimental and toxicologic pathology."},{"issue":"9","key":"pone.0249687.ref093","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1248\/bpb.33.1517","article-title":"Effects of captopril and telmisartan on matrix metalloproteinase-2 and-9 expressions and development of left ventricular fibrosis induced by isoprenaline in rats","volume":"33","author":"M Okada","year":"2010","journal-title":"Biological and Pharmaceutical Bulletin"},{"issue":"1","key":"pone.0249687.ref094","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jcf.2014.06.001","article-title":"Ibuprofen rescues mutant cystic fibrosis transmembrane conductance regulator trafficking","volume":"14","author":"GW Carlile","year":"2015","journal-title":"Journal of Cystic Fibrosis"},{"issue":"5","key":"pone.0249687.ref095","doi-asserted-by":"crossref","DOI":"10.2310\/7070.2007.0049","article-title":"Ibuprofen therapy and nasal polyposis in cystic fibrosis patients","volume":"36","author":"DR Lindstrom","year":"2007","journal-title":"Journal of Otolaryngology"},{"issue":"11","key":"pone.0249687.ref096","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1164\/rccm.200702-181OC","article-title":"Clinical use of ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis","volume":"176","author":"MW Konstan","year":"2007","journal-title":"American journal of respiratory and critical care medicine"},{"issue":"3","key":"pone.0249687.ref097","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jpeds.2007.04.009","article-title":"High-dose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial","volume":"151","author":"LC Lands","year":"2007","journal-title":"The Journal of pediatrics"},{"issue":"13","key":"pone.0249687.ref098","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1056\/NEJM199503303321303","article-title":"Effect of high-dose ibuprofen in patients with cystic fibrosis","volume":"332","author":"MW Konstan","year":"1995","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"pone.0249687.ref099","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nbt1358","article-title":"A quantitative analysis of kinase inhibitor selectivity","volume":"26","author":"MW Karaman","year":"2008","journal-title":"Nature biotechnology"},{"issue":"1","key":"pone.0249687.ref100","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1747-0285.2009.00832.x","article-title":"On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine.","volume":"74","author":"D Tanramluk","year":"2009","journal-title":"Chemical biology & drug design"},{"issue":"2","key":"pone.0249687.ref101","doi-asserted-by":"crossref","first-page":"L354","DOI":"10.1152\/ajplung.2001.280.2.L354","article-title":"Regulation of PDGFR-\u03b1 in rat pulmonary myofibroblasts by staurosporine","volume":"280","author":"PM Lindroos","year":"2001","journal-title":"American Journal of Physiology-Lung Cellular and Molecular Physiology"},{"issue":"9","key":"pone.0249687.ref102","first-page":"2419","article-title":"Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase","volume":"54","author":"G Powis","year":"1994","journal-title":"Cancer research"},{"issue":"6","key":"pone.0249687.ref103","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1091\/mbc.e03-12-0902","article-title":"Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac\/phosphoinositide 3-kinase\/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts","volume":"15","author":"X Shi-Wen","year":"2004","journal-title":"Molecular biology of the cell"},{"issue":"10","key":"pone.0249687.ref104","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0007438","article-title":"Rac inhibition reverses the phenotype of fibrotic fibroblasts.","volume":"4","author":"X Shi-Wen","year":"2009","journal-title":"PLoS One."},{"issue":"10","key":"pone.0249687.ref105","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1038\/jid.2011.156","article-title":"Loss of PTEN expression by dermal fibroblasts causes skin fibrosis","volume":"131","author":"SK Parapuram","year":"2011","journal-title":"Journal of investigative dermatology"},{"issue":"12","key":"pone.0249687.ref106","article-title":"Effects of direct Renin inhibition on myocardial fibrosis and cardiac fibroblast function.","volume":"8","author":"H Zhi","year":"2013","journal-title":"PloS one."},{"issue":"2","key":"pone.0249687.ref107","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s11427-013-4604-z","article-title":"Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart","volume":"57","author":"Y Wang","year":"2014","journal-title":"Science China Life Sciences"},{"issue":"2","key":"pone.0249687.ref108","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s12011-016-0661-z","article-title":"Zinc attenuates tubulointerstitial fibrosis in diabetic nephropathy via inhibition of HIF through PI-3K signaling","volume":"173","author":"X Zhang","year":"2016","journal-title":"Biological trace element research"},{"issue":"10","key":"pone.0249687.ref109","article-title":"Fibulin-1 is increased in asthma\u2013a novel mediator of airway remodeling?","volume":"5","author":"JY Lau","year":"2010","journal-title":"PLoS One."},{"issue":"4","key":"pone.0249687.ref110","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1378\/chest.13-2688","article-title":"Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.","volume":"146","author":"J Jaffar","year":"2014","journal-title":"Chest"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T20:39:13Z","timestamp":1724791153000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249687"}},"subtitle":[],"editor":[{"given":"Christina","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":110,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0249687","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]}}}