{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:13:45Z","timestamp":1792653225123,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"tdm","delay-in-days":0,"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":[[2019,11]]},"abstract":"<jats:p>\n                    Biliary atresia (BA) is a neonatal liver disease featuring cholestasis and severe liver fibrosis (LF). Despite advances in the development of surgical treatment, lacking an early diagnostic marker and intervention of LF invariably leads to death from end\u2010stage liver disease in the early years of life. We previously reported that knockout of sphingosine 1\u2010phosphate receptor 2 (S1PR2) protected mice from bile duct ligation (BDL)\u2010induced cholangiocyte proliferation and LF. Our recent studies further showed that both hepatic and serum exosomal long noncoding RNA H19 (lncRNAH19) levels are correlated with cholestatic injury in multidrug resistance 2 knockout (\n                    <jats:italic toggle=\"yes\">Mdr2\u2013\/\u2013<\/jats:italic>\n                    ) mice. However, the role of lncRNAH19 in BA progression remains unclear. Here, we show that both hepatic and serum exosomal H19 levels are positively correlated with severity of fibrotic liver injuries in BA patients. H19 deficiency protects mice from BDL\u2010induced cholangiocyte proliferation and LF by inhibiting bile\u2010acid\u2013induced expression and activation of S1PR2 and sphingosine kinase 2 (SphK2). Furthermore, H19\u00a0acts as a molecular sponge for members of the microRNA let\u20107 family, which results in up\u2010regulation of high\u2010mobility group AT\u2010hook 2 (HMGA2), a known target of let\u20107 and enhancement of biliary proliferation.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : These results indicate that H19 plays a critical role in cholangiocyte proliferation and cholestatic liver injury in BA by regulating the S1PR2\/SphK2 and let\u20107\/HMGA2 axis. Serum exosomal H19 may represent a noninvasive diagnostic biomarker and potential therapeutic target for BA.\n                  <\/jats:p>","DOI":"10.1002\/hep.30698","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T10:01:12Z","timestamp":1557223272000},"page":"1658-1673","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":130,"title":["Long Noncoding RNA H19 Contributes to Cholangiocyte Proliferation and Cholestatic Liver Fibrosis in Biliary Atresia"],"prefix":"10.1097","volume":"70","author":[{"given":"Yongtao","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery,Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai,China"},{"name":"Shanghai Institute of Pediatric Research,Shanghai,China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runping","family":"Liu","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"}]},{"given":"Xiaojiaoyang","family":"Li","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"}]},{"given":"Emily C.","family":"Gurley","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"}]},{"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"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery,Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai,China"},{"name":"Shanghai Institute of Pediatric Research,Shanghai,China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition,Shanghai,China"}],"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 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