{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:38:25Z","timestamp":1775695105772,"version":"3.50.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Interstitial cystitis\/painful bladder syndrome (IC\/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-\u03b2 (TGF-\u03b2) is thought to be involved in the pathogenesis of IC\/PBS, and previous studies have suggested that administrations of a TGF-\u03b2 inhibitor significantly ameliorated IC\/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC\/PBS has not been comprehensively analyzed. TGF-\u03b2 has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC\/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H\u2082O\u2082) and examined the effects of three TGF-\u03b2 inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-\u03b2 inhibitor treatment improved urinary function and histological changes in the IC\/PBS mouse model, and SB431542 was most effective among the TGF-\u03b2 inhibitors. In our present study, TGF-\u03b2 inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-\u03b2 inhibitor.<\/jats:p>","DOI":"10.1371\/journal.pone.0293983","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T18:24:51Z","timestamp":1699295091000},"page":"e0293983","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["TGF-\u03b2 inhibitor treatment of H\u2082O\u2082-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis\/painful bladder syndrome patients"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1463-8152","authenticated-orcid":true,"given":"Hideto","family":"Taga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsunao","family":"Kishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0809-895X","authenticated-orcid":true,"given":"Yuta","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenta","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichiro","family":"Kotani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsujimoto","family":"Masashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Ukimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osam","family":"Mazda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"issue":"7","key":"pone.0293983.ref001","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/iju.13118","article-title":"Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.","volume":"23","author":"Y Homma","year":"2016","journal-title":"Int J Urol"},{"issue":"2","key":"pone.0293983.ref002","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1053\/eujp.1998.0105","article-title":"Cyclophosphamide cystitis in mice: behavioural characterisation and correlation with bladder inflammation","volume":"3","author":"T Olivar","year":"1999","journal-title":"Eur J Pain"},{"issue":"4","key":"pone.0293983.ref003","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1254\/jphs.12265FP","article-title":"A Novel Mouse Model of Chronic Inflammatory and Overactive Bladder by a Single Intravesical Injection of Hydrogen Peroxide","volume":"121","author":"T Homan","year":"2013","journal-title":"Journal of Pharmacological Sciences"},{"key":"pone.0293983.ref004","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/iju.13972","article-title":"Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis\/bladder pain syndrome","volume":"261","author":"A Furuta","year":"2019","journal-title":"Int J Urol"},{"issue":"9","key":"pone.0293983.ref005","doi-asserted-by":"crossref","first-page":"F1265","DOI":"10.1152\/ajprenal.00042.2013","article-title":"Expression and function of transforming growth factor-\u03b2 isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis","volume":"305","author":"EJ Gonzalez","year":"2013","journal-title":"Am J Physiol Renal Physiol"},{"issue":"13","key":"pone.0293983.ref006","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1113\/JP272148","article-title":"Purinergic signalling underlies transforming growth factor-\u03b2-mediated bladder afferent nerve hyperexcitability","volume":"594","author":"EJ Gonzalez","year":"2016","journal-title":"J Physiol"},{"issue":"10","key":"pone.0293983.ref007","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGF\u03b2 signalling pathway in disease","volume":"11","author":"RJ Akhurst","year":"2012","journal-title":"Nat Rev Drug Discov"},{"issue":"3","key":"pone.0293983.ref008","doi-asserted-by":"crossref","DOI":"10.3390\/biom10030487","article-title":"TGF-\u03b2 Signaling.","volume":"10","author":"K Tzavlaki","year":"2020","journal-title":"Biomolecules"},{"key":"pone.0293983.ref009","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cyto.2018.02.025","article-title":"Blocking TGF-\u03b2 type 1 receptor partially reversed skin tissue damage in experimentally induced atopic dermatitis in mice","volume":"106","author":"A. 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