{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:58:45Z","timestamp":1790006325792,"version":"4.0.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n                    Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells, including cholangiocytes. Exosome\u2010mediated cell\u2010cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies indicate that the long noncoding RNA (lncRNA), H19, is mainly expressed in cholangiocytes, and its aberrant expression is associated with significant down\u2010regulation of small heterodimer partner (SHP) in hepatocytes and cholestatic liver injury in multidrug resistance 2 knockout (Mdr2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice. However, how cholangiocyte\u2010derived H19 suppresses SHP in hepatocytes remains unknown. Here, we report that cholangiocyte\u2010derived exosomes mediate transfer of H19 into hepatocytes and promote cholestatic injury. Hepatic H19 level is correlated with severity of cholestatic injury in both fibrotic mouse models, including Mdr2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, a well\u2010characterized model of primary sclerosing cholangitis (PSC), or CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced cholestatic liver injury mouse models, and human PSC patients. Moreover, serum exosomal\u2010H19 level is gradually up\u2010regulated during disease progression in Mdr2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and patients with cirrhosis. H19\u2010carrying exosomes from the primary cholangiocytes of wild\u2010type (WT) mice suppress SHP expression in hepatocytes, but not the exosomes from the cholangiocytes of H19\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Furthermore, overexpression of H19 significantly suppressed SHP expression at both transcriptional and posttranscriptional levels. Importantly, transplant of H19\u2010carrying serum exosomes of old fibrotic Mdr2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice significantly promoted liver fibrosis (LF) in young Mdr2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Cholangiocyte\u2010derived exosomal\u2010H19 plays a critical role in cholestatic liver injury. Serum exosomal H19 represents a noninvasive biomarker and potential therapeutic target for cholestatic diseases. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018).\n                  <\/jats:p>","DOI":"10.1002\/hep.29838","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T12:02:38Z","timestamp":1518177758000},"page":"599-615","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":136,"title":["Cholangiocyte\u2010derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans"],"prefix":"10.1097","volume":"68","author":[{"given":"Xiaojiaoyang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical 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University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University,Guangzhou,China"},{"name":"China Pharmaceutical University,Nanjing, Jiangsu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4928-3681","authenticated-orcid":false,"given":"Jasmohan S.","family":"Bajaj","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"White","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Pandak","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip B.","family":"Hylemon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-372X","authenticated-orcid":false,"given":"Huiping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center,Virginia Commonwealth University,Richmond,VA"},{"name":"Department of Gastroenterology, the First Affiliated Hospital,Wenzhou Medical 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