{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:46:39Z","timestamp":1767980799714,"version":"3.49.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":132,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Beyond the well\u2010defined role of the Eph (erythropoietin\u2010producing hepatocellular) receptor tyrosine kinases in developmental processes, cell motility, cell trafficking\/adhesion, and cancer, nothing is known about their involvement in liver pathologies. During blood\u2010stage rodent malaria infection we have found that EphB2 transcripts and proteins were up\u2010regulated in the liver, a result likely driven by elevated surface expression on immune cells including macrophages. This was significant for malaria pathogenesis because <jats:italic toggle=\"yes\">EphB2<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice were protected from malaria\u2010induced liver fibrosis despite having a similar liver parasite burden compared with littermate control mice. This protection was correlated with a defect in the inflammatory potential of hepatocytes from <jats:italic toggle=\"yes\">EphB2<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice resulting in a reduction in adhesion molecules, chemokine\/chemokine receptor RNA levels, and infiltration of leukocytes including macrophages\/Kupffer cells, which mediate liver fibrosis during rodent malaria infections. These observations are recapitulated in the well\u2010established carbon tetrachloride model of liver fibrosis in which <jats:italic toggle=\"yes\">EphB2\u2013\/\u2013\n                           <\/jats:italic> carbon tetrachloride\u2013treated mice showed a significant reduction of liver fibrosis compared to carbon tetrachloride\u2013treated littermate mice. Depletion of macrophages by clodronate\u2010liposomes abrogates liver <jats:italic toggle=\"yes\">EphB2<\/jats:italic> messenger RNA and protein up\u2010regulation and fibrosis in malaria\u2010infected mice. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: During rodent malaria, EphB2 expression promotes malaria\u2010associated liver fibrosis; to our knowledge, our data are the first to implicate the EphB family of receptor tyrosine kinases in liver fibrosis or in the pathogenesis of malaria infection. (H<jats:sc>epatology<\/jats:sc> 2015;62:900\u2013914)<\/jats:p>","DOI":"10.1002\/hep.27792","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T00:05:21Z","timestamp":1426637121000},"page":"900-914","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":43,"title":["The receptor tyrosine kinase EphB2 promotes hepatic fibrosis in mice"],"prefix":"10.1097","volume":"62","author":[{"given":"Patrice N.","family":"Mimche","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics,Emory University School of Medicine,Atlanta,GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren M.","family":"Brady","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics,Emory University School of Medicine,Atlanta,GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian 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