{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T10:29:47Z","timestamp":1793788187989,"version":"4.6.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2017R1A6A3A11032024"],"award-info":[{"award-number":["2017R1A6A3A11032024"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF\u20102017R1D1A3B03030521"],"award-info":[{"award-number":["NRF\u20102017R1D1A3B03030521"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Although numerous studies have suggested that canonical I\u03baB kinases (IKK) play a key role in the progression of liver fibrosis, the role of non\u2010canonical IKK\u03b5 and TANK\u2010binding kinase 1 (TBK1) on the development and progression of liver fibrosis remains unclear. To demonstrate such issue, repeated injection of CCl\n                    <jats:sub>4<\/jats:sub>\n                    was used to induce hepatotoxin\u2010mediated chronic liver injury and biliary fibrosis was induced by 0.1% diethoxycarbonyl\u20101, 4\u2010dihydrocollidine diet feeding for 4\u00a0weeks. Mice were orally administered with amlexanox (25, 50, and 100\u00a0mg\/kg) during experimental period. Significantly increased levels of TBK1 and IKK\u03b5 were observed in fibrotic livers or hepatic stellate cells (HSCs) isolated from fibrotic livers. Interestingly, amlexanox treatment significantly inhibited the phosphorylation of TBK1 and IKK\u03b5 accompanied by reduced liver injury as confirmed by histopathologic analysis, decreased serum biochemical levels and fibro\u2010inflammatory responses. Additionally, treatment of amlexanox promoted the fibrosis resolution. In accordance with these findings, amlexanox treatment suppressed HSC activation and its related fibrogenic responses by partially inhibiting signal transducer and activator of transcription 3. Furthermore, amlexanox decreased the activation and inflammatory responses in Kupffer cells. Collectively, we found that inhibition of the TBK1 and IKK\u03b5 by amlexanox is a promising therapeutic strategy to cure liver fibrosis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.14817","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T11:02:39Z","timestamp":1575975759000},"page":"1383-1398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Dual TBK1\/IKK\u025b inhibitor amlexanox attenuates the severity of hepatotoxin\u2010induced liver fibrosis and biliary fibrosis in mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Zixiong","family":"Zhou","sequence":"first","affiliation":[{"name":"Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program) College of Veterinary Medicine Jeonbuk National University Iksan 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