{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:50:11Z","timestamp":1790520611778,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/ http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims:<\/jats:title>\n                    <jats:p>\n                      Janus kinase 2 (JAK2) signaling is increased in human and experimental liver fibrosis with portal hypertension. JAK2 inhibitors, such as pacritinib, are already in advanced clinical development for other indications and might also be effective in liver fibrosis. Here, we investigated the antifibrotic role of the JAK2 inhibitor pacritinib on activated hepatic stellate cells (HSCs)\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and in two animal models of liver fibrosis\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      Transcriptome analyses of JAK2 in human livers and other targets of pacritinib have been shown to correlate with profibrotic factors. Although transcription of JAK2 correlated significantly with\n                      <jats:italic toggle=\"yes\">type I collagen<\/jats:italic>\n                      expression and other profibrotic genes, no correlation was observed for\n                      <jats:italic toggle=\"yes\">interleukin\u20101 receptor\u2010associated kinase<\/jats:italic>\n                      and colony\u2010stimulating factor 1 receptor. Pacritinib decreased gene expression of fibrosis markers in mouse primary and human\u2010derived HSCs\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Moreover, pacritinib decreased the proliferation, contraction, and migration of HSCs. C\n                      <jats:sub>57<\/jats:sub>\n                      BL\/6J mice received ethanol in drinking water (16%) or Western diet in combination with carbon tetrachloride intoxication for 7\u2009weeks to induce alcoholic or nonalcoholic fatty liver disease. Pacritinib significantly reduced liver fibrosis assessed by gene expression and Sirius red staining, as well as HSC activation assessed by alpha\u2010smooth muscle actin immunostaining in fibrotic mice. Furthermore, pacritinib decreased the gene expression of hepatic steatosis markers in experimental alcoholic liver disease. Additionally, pacritinib protected against liver injury as assessed by aminotransferase levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study demonstrates that the JAK2 inhibitor pacritinib may be promising for the treatment of alcoholic and nonalcoholic liver fibrosis and may be therefore relevant for human pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32746","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T06:11:07Z","timestamp":1661148667000},"page":"1228-1240","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":19,"title":["Janus kinase 2 inhibition by pacritinib as potential therapeutic target for liver fibrosis"],"prefix":"10.1097","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-3188","authenticated-orcid":false,"given":"Sandra","family":"Torres","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Cell Death and Proliferation, Instituto Investigaciones Biom\u00e9dicas de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain"},{"name":"Liver Unit\u2010IDIBAPS and Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBERehd), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Bachtler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon D.","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Universit+y Hospital Frankfurt, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Kraus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Schierwagen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hieber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9949-0975","authenticated-orcid":false,"given":"Olaf","family":"Tyc","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Joseph Brol","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Erhard","family":"Uschner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Nijmeijer","sequence":"additional","affiliation":[{"name":"Research and Development Department, Linxis BV, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Welsch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Luise","family":"Berres","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Aachen University Hospital, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garcia\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, Instituto Investigaciones Biom\u00e9dicas de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain"},{"name":"Liver Unit\u2010IDIBAPS and Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBERehd), Barcelona, Spain"},{"name":"Department of Medicine, University of Southern California, Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Carlos","family":"Fernandez\u2010Checa","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, Instituto Investigaciones Biom\u00e9dicas de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain"},{"name":"Liver Unit\u2010IDIBAPS and Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBERehd), Barcelona, Spain"},{"name":"Department of Medicine, University of Southern California, Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Aachen University Hospital, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Vogl","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Universit+y Hospital Frankfurt, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-3881","authenticated-orcid":false,"given":"Jonel","family":"Trebicka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University of M\u00fcnster, M\u00fcnster, Germany"},{"name":"European Foundation for the Study of Chronic Liver Failure \u2013 EF Clif, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"hep32746-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","year":"2005","journal-title":"J Clin Invest"},{"key":"hep32746-bib-0002-20250824","article-title":"Trends and the course of 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fibrosis","volume":"60","year":"2014","journal-title":"Hepatology"},{"key":"hep32746-bib-0006-20250824","first-page":"145","article-title":"Janus\u2010kinase\u20102 relates directly to portal hypertension and to complications in rodent and human cirrhosis","volume":"66","year":"2015","journal-title":"Gut"},{"key":"hep32746-bib-0007-20250824","article-title":"TGR(mREN2)27 rats develop non\u2010alcoholic fatty liver disease\u2010associated portal hypertension responsive to modulations of Janus\u2010kinase 2 and Mas receptor","volume":"9","year":"2019","journal-title":"Sci Rep"},{"key":"hep32746-bib-0008-20250824","article-title":"Rho\u2010kinase inhibitor coupled to peptide\u2010modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats","volume":"9","year":"2019","journal-title":"Sci Rep"},{"key":"hep32746-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"9466","DOI":"10.1096\/fj.201900215RR","article-title":"TG101348, a selective JAK2 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History"}},{"value":"2022-08-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}