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The present research endeavors to elucidate the regulatory mechanisms underpinning this MSU-induced pyroptotic cascade in GA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>J774 cells were exposed to lipopolysaccharide and MSU crystals to establish in vitro GA models, whereas C57BL\/6\u00a0J male mice received MSU crystal injections to mimic in vivo GA conditions. Gene and protein expression levels were evaluated using real-time quantitative PCR, Western blotting, and immunohistochemical assays. Inflammatory markers were quantified via enzyme-linked immunosorbent assays. Pyroptosis was evaluated using immunofluorescence staining for caspase-1 and flow cytometry with caspase-1\/propidium iodide staining. The interaction between MDM2 and PPAR\u03b3 was analyzed through co-immunoprecipitation assays, whereas the interaction between BRD4 and the MDM2 promoter was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. Mouse joint tissues were histopathologically evaluated using hematoxylin and eosin staining.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In GA, PPAR\u03b3 was downregulated, whereas its overexpression mitigated NLRP3 inflammasome activation and pyroptosis. MDM2, which was upregulated in GA, destabilized PPAR\u03b3 through the ubiquitin\u2013proteasome degradation pathway, whereas its silencing attenuated NLRP3 activation by elevating PPAR\u03b3 levels. Concurrently, BRD4 was elevated in GA and exacerbated NLRP3 activation and pyroptosis by transcriptionally upregulating MDM2, thereby promoting PPAR\u03b3 degradation. In vivo experiments showed that BRD4 silencing ameliorated GA through this MDM2\u2013PPAR\u03b3\u2013pyroptosis axis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>BRD4 promotes inflammation and pyroptosis in GA through MDM2-mediated PPAR\u03b3 degradation, underscoring the therapeutic potential of targeting this pathway in GA management.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10020-024-00831-w","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T12:02:18Z","timestamp":1716292938000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["BRD4 promotes gouty arthritis through MDM2-mediated PPAR\u03b3 degradation and pyroptosis"],"prefix":"10.1186","volume":"30","author":[{"given":"Xiaoxia","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4579-5729","authenticated-orcid":false,"given":"Hongbin","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"831_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1476-9255-7-23","volume":"7","author":"NB Bryan","year":"2010","unstructured":"Bryan NB, Dorfleutner A, Kramer SJ, et al. 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