{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:47:09Z","timestamp":1787500029114,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatic fibrosis, characterized by an excessive extracellular matrix (ECM) accumulation, leading to scar\u2010tissue formation is a growing health problem worldwide. Hepatocellular damage due to liver injury triggers inflammation and transdifferentiation of quiescent hepatic stellate cells (HSCs) into proliferative, contractile, and ECM\u2010producing myofibroblasts. Involvement of the Janus kinase (JAK)\u20102 pathway in the pathogenesis of fibrosis has been reported earlier. However, in this study, we have investigated the effect of selective JAK2 antagonist TG101348 in fibroblasts and inflammatory macrophages and\n                    <jats:italic>in vivo<\/jats:italic>\n                    in an acute carbon tetrachloride\u2013induced liver injury mouse model.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , TG101348 significantly inhibited TGF\u2010\u03b2\u2010induced collagen I expression in murine 3T3 fibroblasts. In human HSCs (LX2 cells), TG101348 potently attenuated TGF\u2010\u03b2\u2010induced contractility and the protein and gene expression of major fibrotic parameters (collagen I, vimentin, and \u03b1\u2010smooth muscle actin). In LPS\u2010 and IFN\u2010\u03b3\u2010stimulated inflammatory macrophages, TG101348 significantly reduced the NO release and strongly inhibited the expression of inflammatory markers (inducible nitric oxide synthase, C\u2010C motif chemokine ligand 2, IL\u20101\u03b2, IL\u20106, and C\u2010C chemokine receptor type 2).\n                    <jats:italic>In vivo<\/jats:italic>\n                    in an acute liver injury mouse model, TG101348 significantly attenuated collagen accumulation and HSC activation. Interestingly, TG101348 drastically inhibited macrophage infiltration and intrahepatic inflammation. Pharmacological inhibition of the JAK2 signaling pathway in activated HSCs and inflammatory macrophages using TG101348 suggests a potential therapeutic approach for the treatment of liver fibrosis.\u2014Akcora, B. O., Dathathri, E., Ortiz\u2010Perez, A., Gabri\u00ebl, A. V., Storm, G., Prakash, J., Bansal, R. TG101348, a selective JAK2 antagonist, ameliorates hepatic fibrogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    . FASEB J. 33, 9466\u20139475 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900215rr","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T12:10:45Z","timestamp":1558095045000},"page":"9466-9475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["TG101348, a selective JAK2 antagonist, ameliorates hepatic fibrogenesis\n                    <i>in vivo<\/i>"],"prefix":"10.1096","volume":"33","author":[{"given":"B\u00fcsra \u00d6zt\u00fcrk","family":"Akcora","sequence":"first","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshwari","family":"Dathathri","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ortiz\u2010Perez","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandras Vassilios","family":"Gabri\u00ebl","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Storm","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"},{"name":"Department of Pharmaceutics Utrecht Institute of Pharmaceutical Sciences Faculty of Science Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Bansal","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science and Technology Technical Medical Centre Faculty of Science and Technology University of Twente  Enschede The Netherlands"},{"name":"Department of Pharmacokinetics Toxicology, and Targeting Groningen Research Institute of Pharmacy University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60383-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700613"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070112"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.12.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.104"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.02.026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18272"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051113-024537"},{"key":"e_1_2_8_12_1","first-page":"92","article-title":"Cytokines, STATs and liver disease","volume":"2","author":"Gao B.","year":"2005","journal-title":"Cell. 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