{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T10:01:08Z","timestamp":1775383268799,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Male urethral stricture disease (USD) is predominantly characterized by scar formation. There are few effective therapeutic drugs, and comprehensive molecular characterizations of USD formation remain undefined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The proteomic profiling of twelve scar tissues and five matched normal adjacent tissues (NATs). Proteomic analysis methods were applied to explore the molecular characterizations of USD formation, including uncovering mechanistic pathways and providing novel biomarkers for scar formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Comparative proteomic analysis showed that the extracellular matrix (ECM) and complement cascade signaling were predominant in scar tissues. COL11A1 and CD248 significantly contributed to the accumulation of ECM components. Our study presented diverse molecular mechanisms of scar formation across different ages and suggested the potential effects of PXK in Age 1 (&amp;lt;45) patients. Furthermore, immune infiltration studies indicated the therapeutic potential of inhibiting the complement system (C4A, C4B) in Age 2 (\u226545) patients, providing a potential clinical strategy for USD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study illustrated the pathogenesis of USD formation and the diverse characteristics of USD patients with different ages, enhancing our understanding of the disease\u2019s pathogenesis and providing a valuable resource for USD treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2024.1401970","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T05:00:59Z","timestamp":1721970059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive proteomic characterization of urethral stricture disease in the Chinese population"],"prefix":"10.3389","volume":"11","author":[{"given":"Jiangtao","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengya","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subei","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jijing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1093\/oxfordjournals.jbchem.a123289","article-title":"Effect of calponin on actin-activated myosin ATPase activity","volume":"108","author":"Abe","year":"1990","journal-title":"J. Biochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3588","DOI":"10.1016\/j.cell.2022.08.011","article-title":"Actin cytoskeleton remodeling primes RIG-I-like receptor activation","volume":"185","author":"Acharya","year":"2022","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3978\/j.issn.2223-4683.2014.04.07","article-title":"Epidemiology of urethral strictures","volume":"3","author":"Alwaal","year":"2014","journal-title":"Transl. Androl. Urol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1007\/s43657-022-00070-1","article-title":"Large-scale proteomics data reveal integrated prognosis-related protein signatures and role of SMAD4 and RAD50 in prognosis and immune infiltrations of prostate cancer microenvironment","volume":"2","author":"Anwaier","year":"2022","journal-title":"Phenomics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1189\/jlb.3A0614-280R","article-title":"Macrophage migration inhibitory factor is required for recruitment of scar-associated macrophages during liver fibrosis","volume":"97","author":"Barnes","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1242\/jcs.111.13.1791","article-title":"Actin microfilaments control the MHC class II antigen presentation pathway in B cells","volume":"111","author":"Barois","year":"1998","journal-title":"J. Cell Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12890-016-0211-7","article-title":"Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis","volume":"16","author":"Bartis","year":"2016","journal-title":"BMC Pulm. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1097\/DSS.0000000000000819","article-title":"Keloids and hypertrophic scars: pathophysiology, classification, and treatment","volume":"43","author":"Berman","year":"2017","journal-title":"Dermatol Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.juro.2014.07.007","article-title":"Lower urinary tract pain and anterior urethral stricture disease: prevalence and effects of urethral reconstruction","volume":"193","author":"Bertrand","year":"2015","journal-title":"J. Urol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s43657-022-00073-y","article-title":"Skin microbiome, metabolome and skin Phenome, from the perspectives of skin as an ecosystem","volume":"2","author":"Chen","year":"2022","journal-title":"Phenomics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"794451","DOI":"10.3389\/fpubh.2021.794451","article-title":"The changing trend in clinical characteristics and outcomes of male patients with urethral stricture over the past 10 Years in China","volume":"9","author":"Cheng","year":"2021","journal-title":"Front. Public Health"},{"key":"B12","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12933-021-01322-6","article-title":"The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats","volume":"20","author":"Daud","year":"2021","journal-title":"Cardiovasc Diabetol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"475","DOI":"10.18632\/aging.100772","article-title":"Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice","volume":"7","author":"Demyanenko","year":"2015","journal-title":"Aging (Albany NY)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature12783","article-title":"Distinct fibroblast lineages determine dermal architecture in skin development and repair","volume":"504","author":"Driskell","year":"2013","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.3389\/fimmu.2019.01936","article-title":"Clinical and genetic spectrum of a large cohort with total and sub-total complement deficiencies","volume":"10","author":"El Sissy","year":"2019","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1126\/science.274.5289.998","article-title":"Laser capture microdissection","volume":"274","author":"Emmert-Buck","year":"1996","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1007\/s11255-011-9940-y","article-title":"Etiology and current clinical characteristics of male urethral stricture disease: experience from a public teaching hospital in Senegal","volume":"43","author":"Fall","year":"2011","journal-title":"Int. Urology Nephrol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/nbt.3825","article-title":"Firmiana: towards a one-stop proteomic cloud platform for data processing and analysis","volume":"35","author":"Feng","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1038\/s41467-018-03121-2","article-title":"A proteomic landscape of diffuse-type gastric cancer","volume":"9","author":"Ge","year":"2018","journal-title":"Nat. Commun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1089\/end.2018.0316","article-title":"Urethral stricture disease: evaluation of the male urethra","volume":"34","author":"Gelman","year":"2020","journal-title":"J. Endourology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1158\/1078-0432.CCR-17-1558","article-title":"A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of monotherapy ontuxizumab (MORAb-004) plus best supportive care in patients with chemorefractory metastatic colorectal cancer","volume":"24","author":"Grothey","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nrurol.2013.275","article-title":"Male urethral strictures and their management","volume":"11","author":"Hampson","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1080\/08941939.2021.1880672","article-title":"Deletion of calponin 2 reduces the formation of postoperative peritoneal adhesions","volume":"35","author":"Hsieh","year":"2022","journal-title":"J. Invest. Surg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41586-019-0987-8","article-title":"C. Chinese Human Proteome Project: proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma","volume":"567","author":"Jiang","year":"2019","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"D1211","DOI":"10.1093\/nar\/gky869","article-title":"iProX: an integrated proteome resource","volume":"47","author":"Jie","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nrc1877","article-title":"Fibroblasts in cancer","volume":"6","author":"Kalluri","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.600840","article-title":"Human cerebral cortex proteome of fragile X-associated tremor\/ataxia syndrome","author":"Katharine Nichole","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1080\/09546634.2019.1610550","article-title":"Combination of pulsed dye laser and verapamil in comparison with verapamil alone in the treatment of keloid","volume":"31","author":"Khattab","year":"2020","journal-title":"J. Dermatol. Treat."},{"key":"B30","doi-asserted-by":"publisher","first-page":"19212","DOI":"10.1021\/acsami.2c02549","article-title":"Novel synthetic polymer-based 3D contraction assay: a versatile preclinical research platform for fibrosis","volume":"14","author":"Kumari","year":"2022","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B31","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/s41467-021-27667-w","article-title":"Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity","volume":"13","author":"Lam","year":"2022","journal-title":"Nat. Commun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1104\/pp.16.00992","article-title":"Capping protein modulates actin remodeling in response to reactive oxygen species during plant innate immunity","volume":"173","author":"Li","year":"2017","journal-title":"Plant Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1038\/s41467-023-37221-5","article-title":"Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes","volume":"14","author":"Lingling","year":"","journal-title":"Nat. Commun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1038\/s41467-023-37440-w","article-title":"Integrative proteogenomic characterization of early esophageal cancer","volume":"14","author":"Lingling","year":"","journal-title":"Nat. Commun."},{"key":"B35","first-page":"54","article-title":"When the disaster drill is for real","volume":"55","author":"Lippman","year":"1992","journal-title":"RN"},{"key":"B36","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.eururo.2021.05.022","article-title":"European association of urology guidelines on urethral stricture disease (Part 1): management of male urethral stricture disease","volume":"80","author":"Lumen","year":"2021","journal-title":"Eur. Urol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.eururo.2010.11.015","article-title":"Urethroplasty for strictures after phallic reconstruction: a single-institution experience","volume":"60","author":"Lumen","year":"2011","journal-title":"Eur. Urol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/hep.32624","article-title":"Proteogenomic characterization of cholangiocarcinoma","volume":"77","author":"Mengjie","year":"2022","journal-title":"Hepatology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s43657-021-00036-9","article-title":"Recent advances in understanding of alzheimer\u2019s disease progression through mass spectrometry-based metabolomics","volume":"2","author":"Mill","year":"2022","journal-title":"Phenomics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1165\/rcmb.2015-0009OC","article-title":"Disruption of calcium signaling in fibroblasts and attenuation of bleomycin-induced fibrosis by nifedipine","volume":"53","author":"Mukherjee","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.urology.2012.08.062","article-title":"Contemporary urethral stricture characteristics in the developed world","volume":"81","author":"Palminteri","year":"2013","journal-title":"Urology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"80","DOI":"10.5173\/ceju.2020.0050","article-title":"Calibration of urethra with anti-scar gel as a new preventive method for stricture recurrence after urethroplasty performed due to refractory anterior urethral stricture disease","volume":"73","author":"Perdzynski","year":"2020","journal-title":"Central Eur. J. Urology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.3389\/fphar.2020.01201","article-title":"Relaxin can mediate its anti-fibrotic effects by targeting the myofibroblast NLRP3 inflammasome at the level of caspase-1","volume":"11","author":"Pinar","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"983501","DOI":"10.3389\/fimmu.2022.983501","article-title":"The anti-aging effects of Renshen Guben on thyrotoxicosis mice: improving immunosenescence, hypoproteinemia, lipotoxicity, and intestinal flora","volume":"13","author":"Qin","year":"2022","journal-title":"Front. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/nrneph.2017.156","article-title":"The renaissance of complement therapeutics","volume":"14","author":"Ricklin","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"aaa2151","DOI":"10.1126\/science.aaa2151","article-title":"Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential","volume":"348","author":"Rinkevich","year":"2015","journal-title":"Science"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1016\/j.juro.2007.01.041","article-title":"Male urethral stricture disease","volume":"177","author":"Santucci","year":"2007","journal-title":"J. Urology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"9137892","DOI":"10.1155\/2018\/9137892","article-title":"The benefits of using a small caliber ureteroscope in evaluation and management of urethral stricture","volume":"2018","author":"Shahrour","year":"2018","journal-title":"Adv. Urol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"973","DOI":"10.4049\/jimmunol.117.3.973","article-title":"Humoral immunostimulation","volume":"117","author":"Shearer","year":"1976","journal-title":"J. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1128\/iai.11.2.273-279.1975","article-title":"Interaction of complex polysaccharides with the complement system: effect of calcium depletion on terminal component consumption","volume":"11","author":"Snyderman","year":"1975","journal-title":"Infect. Immun."},{"key":"B51","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1111\/j.1464-410X.2012.11600.x","article-title":"A geographic analysis of male urethral stricture aetiology and location","volume":"112","author":"Stein","year":"2013","journal-title":"Bju Int."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1128\/MCB.01105-09","article-title":"Characterization of PXK as a protein involved in epidermal growth factor receptor trafficking","volume":"30","author":"Takeuchi","year":"2010","journal-title":"Mol. Cell Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"D1522","DOI":"10.1093\/nar\/gkab1081","article-title":"iProX in 2021: connecting proteomics data sharing with big data","volume":"50","author":"Tao","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12917-017-1003-x","article-title":"FOXO1, PXK, PYCARD and SAMD9L are differentially expressed by fibroblast-like cells in equine synovial membrane compared to joint capsule","volume":"13","author":"Thomsen","year":"2017","journal-title":"BMC Vet. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1186\/s13287-018-1035-6","article-title":"Urothelium with barrier function differentiated from human urine-derived stem cells for potential use in urinary tract reconstruction","volume":"9","author":"Wan","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1002\/pmic.201200017","article-title":"LFQuant: a label-free fast quantitative analysis tool for high-resolution LC-MS\/MS proteomics data","volume":"12","author":"Wei","year":"2012","journal-title":"Proteomics"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1136\/gutjnl-2014-308325","article-title":"CD248\/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism","volume":"65","author":"Wilhelm","year":"2016","journal-title":"Gut"},{"key":"B58","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/path.2277","article-title":"Cellular and molecular mechanisms of fibrosis","volume":"214","author":"Wynn","year":"2008","journal-title":"J. Pathol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.3892\/ijmm.2018.3487","article-title":"microRNA expression profiles of scar and normal tissue from patients with posterior urethral stricture caused by pelvic fracture urethral distraction defects","volume":"41","author":"Zhang","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3892\/ijmm.2016.2816","article-title":"Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-\u03b21\/Smad3 pathway","volume":"39","author":"Zhao","year":"2017","journal-title":"Int. J. Mol. Med."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1401970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T05:01:06Z","timestamp":1721970066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1401970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":60,"alternative-id":["10.3389\/fmolb.2024.1401970"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2024.1401970","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"article-number":"1401970"}}