{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:57:30Z","timestamp":1785488250362,"version":"3.56.0"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Natural Science Foundation of Shanxi Province","award":["202503021211298"],"award-info":[{"award-number":["202503021211298"]}]},{"name":"The Scientific Research Project of Shanxi Provincial Health Commission","award":["2022073"],"award-info":[{"award-number":["2022073"]}]},{"name":"The Open Project of the Key Laboratory of Medical Molecular Virology of the Ministry of Education of China\/Health Commission of China at Fudan University","award":["FDMV-2021004"],"award-info":[{"award-number":["FDMV-2021004"]}]},{"name":"The General Teaching Reform Innovation Project of Shanxi Province Higher Education Institutions of Shanxi Provincial Department of Education","award":["J20230474"],"award-info":[{"award-number":["J20230474"]}]},{"name":"The College Student Innovation and Entrepreneurship Training Program of Shanxi Province","award":["20240410"],"award-info":[{"award-number":["20240410"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_med-2026-1476_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to explore the regulatory role of the TP63 gene in interstitial cystitis (IC) and its molecular mechanism of involvement in disease occurrence and development through the pyroptosis pathway through single-cell sequencing and bioinformatics analysis, and evaluate its potential as a therapeutic target and biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_med-2026-1476_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 6\u20138\u00a0week SPF grade female SD rat IC model was constructed by intraperitoneal injection of cyclophosphamide (n=10\/group, repeated 3 times). The model construction effect was verified by the Von Frey fiber tenderness method, urodynamic evaluation, and bladder histopathological analysis. Screening key genes related to apoptosis in bladder tissue of IC rats using single-cell sequencing and bioinformatics analysis.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments were conducted using lipopolysaccharide (LPS) to treat immortalized human ureteral epithelial cells (SV-HUC-1) to establish a cellular inflammation model (n=6\/group, repeated 3 times), and the transcription level changes of the TP63 gene were detected by RT-PCR. Western blotting was used to detect the expression of apoptosis-related proteins and NF-\u03baB\/NLRP3\/caspase-1 signaling pathway proteins (caspase-1, GSDMD, ASC) in the bladder tissue of IC rats. The CCK8 method and EdU experiment were used to evaluate cell survival rate and proliferation ability, respectively. ChIP-qPCR was conducted to detect the binding of TP63 to the RELA promoter region. The role of caspase-1 in the pyroptosis pathway was verified using the caspase-1 inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_med-2026-1476_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single-cell sequencing and bioinformatics analysis showed that the TP63 gene was significantly upregulated in the bladder tissue of IC rats (p&lt;0.0001). Western blotting results showed a significant increase in the expression of apoptosis-related proteins in the IC model (p&lt;0.0001), while HE staining showed a significant increase in the infiltration of mast cells, macrophages, and T\u00a0cells (p&lt;0.05).\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments, Western blotting results showed that after LPS intervention, the expression of NLRP3 inflammasome component (ASC) and downstream effector molecule (GSDMD) in SV-HUC-1 increased, the apoptotic characteristic protein caspase-1 was activated, CCK-8 detected a decrease in cell viability, and Edu experiments showed inhibition of cell proliferation. After TP63 siRNA intervention, all the above effects were reversed. ChIP-qPCR confirmed that TP63 directly binds to the RELA promoter region, activating NF-\u03baB signaling. Furthermore, caspase-1 inhibition experiments demonstrated that suppressing caspase-1 significantly alleviated TP63-mediated pyroptosis and inflammatory responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_med-2026-1476_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TP63 contributes to the pathogenesis of IC by directly binding to the RELA promoter, activating NF-\u03baB signaling, and subsequently regulating the NLRP3\/caspase-1\/GSDMD axis to induce bladder epithelial cell pyroptosis. TP63 shows promise as a potential biomarker and therapeutic target for\u00a0IC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/med-2026-1476","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T07:59:18Z","timestamp":1785484758000},"source":"Crossref","is-referenced-by-count":0,"title":["TP63 regulates pyroptosis via NF-\u03baB\/NLRP3\/caspase-1 signaling in interstitial cystitis: insights from single-cell sequencing"],"prefix":"10.1515","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9977-0592","authenticated-orcid":false,"given":"Wantong","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Urology , The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People\u2019s Hospital) , Taiyuan City , Shanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3006-9057","authenticated-orcid":false,"given":"Minli","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology , The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People\u2019s Hospital) , Taiyuan City , Shanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-8245","authenticated-orcid":false,"given":"Lei","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Urology , The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People\u2019s Hospital) , Taiyuan City , Shanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026073107591235378_j_med-2026-1476_ref_001","doi-asserted-by":"crossref","unstructured":"Li, J, Yi, X, Ai, J. 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