{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:26:37Z","timestamp":1740104797344,"version":"3.37.3"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,7,16]],"date-time":"2023-07-16T00:00:00Z","timestamp":1689465600000},"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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>N6\u2010methyladenosine (m6A) modification is a critical posttranscriptional event in gene regulation. Thus, identifying methyltransferase, demethylase, or m6A binding protein\u2010mediated m6A modifications in cancer or noncancer transcriptomes has become a promising novel strategy for disease therapy development. However, novel insights into m6A modification in partial bladder outlet obstruction (pBOO) and detailed information about the drivers of bladder remodeling remain to be elucidated. Here, we first characterized the m6A modification landscape in pBOO and investigated potential actionable pharmaceutical targets for future therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated an improved animal model of pBOO in SD rats with urethral meatus stricture induced by suturing. Urodynamic investigations and cystometry were carried out to evaluate the physiologic changes elicited by pBOO. Whole\u2010transcriptome sequencing (RNA\u2010seq) and m6A\u2010modified RNA immunoprecipitation sequencing (MeRIP\u2010seq) were subsequently performed to analyze the expression pattern associated with bladder remodeling in pBOO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cystometric evaluation of bladder function demonstrated obvious increases in pressure\u2010related parameters in the pBOO group. Hematoxylin and eosin\u00a0staining and Masson's trichrome staining validated the occurrence of bladder remodeling. A global elevation in m6A RNA methylation levels was observed in parallel to a increased expression of METTL3 in the pBOO group. High\u2010throughput sequencing revealed the differences in expression patterns between the pBOO and sham\u2010operated groups. Furthermore, potential m6A\u2010modified genes, including CCN2, may serve as new pharmaceutical targets to reverse bladder remodeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Exploring the roles of m6A\u2010modified genes identified as associated with bladder remodeling by integrating RNA\u2010seq and MeRIP\u2010seq data can offer new insights for developing promising treatments for pBOO patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.25233","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T06:46:57Z","timestamp":1689576417000},"page":"1506-1521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["METTL3\u2010dependent m6A modification mediates bladder remodeling after partial bladder outlet obstruction through CCN2 activation"],"prefix":"10.1002","volume":"42","author":[{"given":"Yafei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Urology, The Eighth Affiliated Hospital Sun Yat\u2010sen University Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3397-009X","authenticated-orcid":false,"given":"Jun","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Chengdu University  Chengdu Sichuan China"},{"name":"Graduate School Zunyi Medical University  Zunyi Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Chengdu University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanxiong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, The Eighth 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