{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:40:22Z","timestamp":1792428022740,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2022NSFSC1308"],"award-info":[{"award-number":["2022NSFSC1308"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["24NSFSC7707"],"award-info":[{"award-number":["24NSFSC7707"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2009100"],"award-info":[{"award-number":["2021YFC2009100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2009102"],"award-info":[{"award-number":["2021YFC2009102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner\u2010type interstitial cystitis\/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single\u2010cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A\n                    <jats:sup>+<\/jats:sup>\n                    umbrella cells and a simultaneous increase in progenitor\u2010like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A\n                    <jats:sup>+<\/jats:sup>\n                    umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A\n                    <jats:sup>+<\/jats:sup>\n                    umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A\n                    <jats:sup>+<\/jats:sup>\n                    umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A\n                    <jats:sup>+<\/jats:sup>\n                    umbrella cells in HIC urothelium. Finally, we conducted\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments to confirm the potential of the TLR3\u2013NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self\u2010repair strategies for HIC patients. \u00a9 2024 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6275","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T04:33:58Z","timestamp":1711686838000},"page":"203-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<scp>UPK3A<\/scp>\n                    <sup>+<\/sup>\n                    umbrella cell damage mediated by\n                    <scp>TLR3\u2013NR2F6<\/scp>\n                    triggers programmed destruction of urothelium in Hunner\u2010type interstitial cystitis\/painful bladder syndrome"],"prefix":"10.1002","volume":"263","author":[{"given":"Liao","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu Sichuan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu Sichuan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu Sichuan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu Sichuan PR 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