{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T18:04:09Z","timestamp":1778781849093,"version":"3.51.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T00:00:00Z","timestamp":1537747200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>Long noncoding RNA (lncRNA) H19 is abundantly expressed in fetal liver. Its expression is significantly diminished in adult healthy liver but is re\u2010induced in chronic liver diseases, including cholestasis. In this study, we developed a new method with combined<jats:bold>in situ<\/jats:bold>hybridization (ISH) and immunofluorescence (IF) colabeling to establish an H19 expression profile with both parenchymal and nonparenchymal cell\u2010specific markers in the livers of cholestatic mouse models and patients with cholestasis.<jats:italic toggle=\"yes\">H19<\/jats:italic>RNA<jats:sup>+<\/jats:sup>cells showed no colocalization with biliary epithelial cell marker cytokeratin 19 (CK19)<jats:sup>+<\/jats:sup>cholangiocytes but were immediately adjacent to biliary structures in bile duct ligation (BDL), 3,5\u2010diethoxycarbony1\u20101,4\u2010dihydrocollidine (DDC), and multidrug\u2010resistant gene 2 knockout (<jats:bold>Mdr2 \u2013\/\u2013<\/jats:bold>) mouse models and in human primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) liver specimens. In contrast, double\u2010positive<jats:italic toggle=\"yes\">H19<\/jats:italic>RNA<jats:sup>+<\/jats:sup>\/sex\u2010determining region Y (SRY)\u2010box 9 (SOX9)<jats:sup>+<\/jats:sup>ductal progenitor cells,<jats:italic toggle=\"yes\">H19<\/jats:italic>RNA<jats:sup>+<\/jats:sup>\/hepatocyte nuclear factor 4\u03b1 (HNF4\u03b1)<jats:sup>+<\/jats:sup>hepatocytes,<jats:italic toggle=\"yes\">H19<\/jats:italic>RNA<jats:sup>+<\/jats:sup>\/F4\/80<jats:sup>+<\/jats:sup>Kupffer cells, HNF4\u03b1<jats:sup>+<\/jats:sup>\/SOX9<jats:sup>+<\/jats:sup>hybrid hepatocytes, as well as triple\u2010positive<jats:bold>H19<\/jats:bold>RNA<jats:sup>+<\/jats:sup>\/HNF4\u03b1<jats:sup>+<\/jats:sup>\/SOX9<jats:sup>+<\/jats:sup>periportal hepatocytes were identified. In addition,<jats:bold>H19<\/jats:bold>RNA could not be detected in mesenchymal cell marker desmin<jats:sup>+<\/jats:sup>cells. Furthermore,<jats:bold>H19<\/jats:bold>RNA was predominately detected in cytoplasm with a small amount at the interspace with neighboring cells.<jats:bold>Conclusion:<\/jats:bold><jats:italic toggle=\"yes\">H19<\/jats:italic>RNA is localized in HNF4\u03b1<jats:sup>+<\/jats:sup>periportal hepatocytes, SOX9<jats:sup>+<\/jats:sup>ductal progenitor cells, and F4\/80<jats:sup>+<\/jats:sup>Kupffer cells but not in CK19<jats:sup>+<\/jats:sup>cholangiocytes and desmin<jats:sup>+<\/jats:sup>stellate cells in cholestatic livers.<\/jats:p>","DOI":"10.1002\/hep4.1252","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T09:17:20Z","timestamp":1537780640000},"page":"1356-1368","source":"Crossref","is-referenced-by-count":14,"title":["H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4\u03b1+ Periportal Hepatocytes but Not Cytokeratin 19+ Cholangiocytes in Cholestatic Livers"],"prefix":"10.1097","volume":"2","author":[{"given":"YanChao","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Physiology and Neurobiology and the Institute of Systems Genomics,University of Connecticut,Storrs,CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology and the Institute of Systems Genomics,University of Connecticut,Storrs,CT"},{"name":"School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ShiYing","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liver Center,Yale University,New Haven,CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YongFeng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology and the Institute of Systems Genomics,University of Connecticut,Storrs,CT"},{"name":"Department of Endocrinology and Metabolism,Shandong Provincial Hospital\/Shandong University,Jinan,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liver Center,Yale University,New Haven,CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"KeZhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics,Wayne State University School of Medicine,Detroit,MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,Shandong Provincial Hospital\/Shandong University,Jinan,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JiaJun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,Shandong Provincial Hospital\/Shandong University,Jinan,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WenDong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute,Beckman Research Institute, City of Hope National Medical Center,Duarte,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suthat","family":"Liangpunsakul","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of 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