{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:00:00Z","timestamp":1792512000157,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Partial bladder outlet obstruction (pBOO) may lead to bladder remodeling, including fibrosis and extracellular matrix (ECM) deposition. Despite the extensive research on the mechanisms underlying pBOO, potential therapeutic targets for the treatment of pBOO require further research. Dysregulated expression of thrombospondin\u20101 (Thbs1) has been reported in various human fibrotic diseases; however, its relationship with pBOO remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>Investigate the effects of Thbs1 on bladder remodeling caused by pBOO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established a pBOO model in Sprague\u2013Dawley rats and performed urodynamic analyses to estimate functional changes in the bladder, validated the histopathological changes in the bladder by using haematoxylin\u2013eosin and Masson's trichrome staining, identified key target genes by integrating RNA sequencing\u00a0(RNA\u2010seq) and bioinformatics analyses, validated the expression of related factors using Western blot analysis and RT\u2010qPCR, and used immunofluorescence staining to probe the potential interaction factors of Thbs1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urodynamic results showed that pressure\u2010related parameters were significantly increased in rats with pBOO. Compared with the sham group, the pBOO group demonstrated significant increases in bladder morphology, bladder weight, and collagen deposition. Thbs1 was significantly upregulated in the bladder tissues of rats with pBOO, consistent with the RNA\u2010seq data. Thbs1 upregulation led to increased expression of matrix metalloproteinase (MMP) 2, MMP9, and fibronectin (Fn) in normal human urinary tract epithelial cells (SV\u2010HUC\u20101), whereas anti\u2010Thbs1 treatment inhibited the production of these cytokines in TGF\u2010\u03b21\u2010treated SV\u2010HUC\u20101. Further experiments indicated that Thbs1 affected bladder remodeling in pBOO via the fibroblast growth factor receptor 3 (FGFR3) pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Thbs1 plays a crucial role in bladder remodeling caused by pBOO. Targeting Thbs1 might alleviate ECM damage. Mechanistically, Thbs1 may function via the FGFR signaling pathway by regulating the FGFR3 receptor, identified as the most relevant disease target of pBOO, and FGF2 may be a mediator. These findings suggest that Thbs1 plays a role in BOO development and is a therapeutic target for this condition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.25366","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:44:24Z","timestamp":1702910664000},"page":"516-526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3\/p\u2010FGFR3 pathway"],"prefix":"10.1002","volume":"43","author":[{"given":"Jun","family":"Long","sequence":"first","affiliation":[{"name":"Clinical Medical College &amp; Affiliated Hospital of Chengdu University Chengdu China"},{"name":"Graduate School Zunyi Medical University Zunyi Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology The Eighth Affiliated Hospital of Sun Yat\u2010sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Medical College &amp; 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Affiliated Hospital of Chengdu University Chengdu China"},{"name":"Graduate School Zunyi Medical University Zunyi Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-018-0329-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09993.x"},{"issue":"10","key":"e_1_2_12_4_1","first-page":"832","article-title":"Progress in research on bladder outlet obstruction","volume":"35","author":"Bowen S","year":"2020","journal-title":"J Clin Urol"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488407"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314962"},{"key":"e_1_2_12_7_1","first-page":"1275","article-title":"Role of thrombospondin\u20111 and thrombospondin\u20112 in cardiovascular diseases (Review)","volume":"45","author":"Zhang K","year":"2020","journal-title":"Int J Mol Med"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226854"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.744239"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.24896"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107947"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23427"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09445.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12071002"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.12.009"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.03.112"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2605"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-104802"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12749"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.630228"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.10.002"},{"key":"e_1_2_12_22_1","first-page":"720","article-title":"Update of fibroblast growth factor receptor signaling pathway in sarcoma","volume":"9","author":"Wen\u2010ya Z","year":"2015","journal-title":"Chinese J Bone Joint"},{"key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/6026719","article-title":"Effect of sulforaphane on bladder compliance in a rat model of partial bladder outlet obstruction","volume":"2019","author":"Liu C","year":"2019","journal-title":"Oxid Med Cell Longevity"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10824"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107618"}],"container-title":["Neurourology and Urodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.25366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T12:47:43Z","timestamp":1710420463000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/nau.25366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/nau.25366"],"URL":"https:\/\/doi.org\/10.1002\/nau.25366","archive":["Portico"],"relation":{},"ISSN":["0733-2467","1520-6777"],"issn-type":[{"value":"0733-2467","type":"print"},{"value":"1520-6777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]},"assertion":[{"value":"2023-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}