{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:29:43Z","timestamp":1786685383277,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2023GXNSFAA026210"],"award-info":[{"award-number":["2023GXNSFAA026210"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2024GXNSFAA010388"],"award-info":[{"award-number":["2024GXNSFAA010388"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hyperuricemia, characterized by elevated serum uric acid (SUA) levels, is increasingly recognized as a pathological contributor to renal injury through oxidative stress, inflammation, and apoptosis. Hirudin, a thrombin inhibitor derived from leech saliva, has recently been noted for its anti\u2010inflammatory properties, yet its role in hyperuricemia remains unclear. This study aimed to investigate the protective effects and underlying mechanisms of hirudin in a uric acid (UA)\u2010induced renal tubular epithelial injury model. Using HK\u20102 cells, we found that hirudin enhanced cell viability and reduced apoptosis in UA\u2010treated conditions. Mechanistically, these protective effects were mediated through downregulation of TNFRSF6B, a decoy receptor involved in inflammatory and apoptotic signaling. TNFRSF6B knockdown potentiated hirudin's cytoprotective effects, whereas its overexpression reversed them. Hirudin treatment attenuated UA\u2010induced expression of urate transporters (URAT1, GLUT9, and OAT4) and pro\u2010inflammatory cytokine IL\u20101\u03b2, both at the transcriptional and protein levels. Moreover, hirudin suppressed activation of the NF\u2010\u03baB signaling pathway, a critical mediator of inflammation and apoptosis in hyperuricemia, with transcriptomic and immunoblotting data confirming downregulation of NF\u2010\u03baB\u2010associated targets. Co\u2010treatment with JSH\u201023, an NF\u2010\u03baB inhibitor, further reinforced these findings and highlighted a TNFRSF6B\/NF\u2010\u03baB axis as a key regulatory mechanism. Collectively, these findings reveal a novel protective role for hirudin in UA\u2010induced renal injury, mediated via modulation of TNFRSF6B and suppression of NF\u2010\u03baB signaling. This study provides new insight into the potential therapeutic application of hirudin in hyperuricemia\u2010associated kidney damage.<\/jats:p>","DOI":"10.1002\/prp2.70305","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:14:03Z","timestamp":1785557643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hirudin Attenuates Uric Acid\u2010Induced Renal Tubular Injury via\n                    <scp>TNFRSF6B<\/scp>\n                    \u2010Mediated Suppression of\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Signaling"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6121-7173","authenticated-orcid":false,"given":"Yingxue","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmacy Jiangbin Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9595-9295","authenticated-orcid":false,"given":"Yongjie","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jiangbin Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanzhi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jiangbin Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jiangbin Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jiangbin Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangxi Keyken Technology Group Co., Ltd.  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