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Using a rat model of GA established through potassium oxonate and yeast gavage combined with intra-articular monosodium urate (MSU) injection, we isolated and characterized plasma exosomes using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Differential exosomal protein expression was analyzed using 4D label-free proteomics technology, followed by GO and KEGG enrichment analyses, and protein\u2013protein interaction (PPI) network construction to identify core targets. In vivo experiments measured the expression levels of CTSD in synovial tissues and joint fluid, as well as HPRT1 in renal tissues, while in vitro experiments involved co-culturing NRK cells with exosomes to validate target protein expression. The results indicated that serum uric acid levels were significantly elevated in the model group (p &lt; 0.01), accompanied by pronounced joint swelling and inflammation. Exosome characterization confirmed their typical bilayer membrane structure and the expression of marker proteins (CD63\/TSG101). Proteomic analysis identified 40 differentially expressed proteins (12 upregulated and 28 downregulated) enriched in pathways such as complement and coagulation cascades, autophagy, lysosomal function, and purine metabolism. In vivo and in vitro experiments demonstrated significantly increased CTSD expression (p &lt; 0.05\/p &lt; 0.01) and decreased HPRT1 expression (p &lt; 0.05\/p &lt; 0.01) in the model group, suggesting that exosomes are involved in the occurrence and development of GA by regulating purine metabolism and lysosomal dysfunction. These findings offer new insights into disease mechanisms and potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms26115320","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring Exosome Contributions to Gouty Arthritis: A Proteomics and Experimental Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Chengjin","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-3742","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Pharmacovigilance and Rational Use of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-068X","authenticated-orcid":false,"given":"Zhijian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,1]]},"reference":[{"key":"ref_1","first-page":"3160","article-title":"Modern cognition and prevention and treatment of uric acid metabolism disorders-related diseases with traditional Chinese medicine","volume":"49","author":"Wang","year":"2024","journal-title":"J. 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