{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:55:17Z","timestamp":1786589717233,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31671080"],"award-info":[{"award-number":["31671080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Septic acute kidney injury (AKI) is the most common AKI syndrome in the intensive care unit (ICU), and it accounts for approximately half of AKI cases. Tofacitinib (TOFA) is a pan\u2010Janus kinase (JAK) inhibitor that exhibits potent anti\u2010inflammatory activity in rheumatoid arthritis. However, no study has examined the functional role of TOFA in septic AKI. In the present study, we investigated the protective effects of TOFA on septic AKI and the underlying mechanisms. A lipopolysaccharide\u2010 (LPS\u2010) induced AKI model was established in C57BL\/6 mice via an intraperitoneal injection of LPS (10\u2009mg\/kg). One hour after LPS challenge, the mice were orally administered TOFA (5, 10, or 15\u2009mg\/kg) every 6\u2009h until sacrifice at 24\u2009h. We found that TOFA significantly ameliorated LPS\u2010induced renal histopathological changes and dysfunction. TOFA also suppressed the expression levels of proinflammatory cytokines (TNF\u2010<jats:italic>\u03b1<\/jats:italic>, IL\u20101<jats:italic>\u03b2<\/jats:italic>, IL\u20106, and IFN\u2010<jats:italic>\u03b3<\/jats:italic>) and the parameters of oxidative stress (MDA, GSH, SOD, and CAT) in kidney tissues. These results may be associated with the inhibitory effect of TOFA on the JAK\u2010STAT1\/STAT3 pathway, which was significantly activated by LPS challenge. TOFA treatment also inhibited LPS\u2010induced activation of the TLR4\/NF\u2010<jats:italic>\u03ba<\/jats:italic>B pathway. In conclusion, we revealed that TOFA had a protective effect on LPS\u2010induced AKI, and it may be a promising therapeutic agent for septic AKI.<\/jats:p>","DOI":"10.1155\/2021\/8877056","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T17:50:10Z","timestamp":1610733010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Tofacitinib Ameliorates Lipopolysaccharide\u2010Induced Acute Kidney Injury by Blocking the JAK\u2010STAT1\/STAT3 Signaling 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