{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:51:31Z","timestamp":1791219091723,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T00:00:00Z","timestamp":1578700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK104893"],"award-info":[{"award-number":["DK104893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK-057543;  AA026629"],"award-info":[{"award-number":["DK-057543;  AA026629"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000938","name":"Department of Veterans' Affairs, Australian Government","doi-asserted-by":"publisher","award":["I01BX004033;I01BX001390; IK6BX004477)."],"award-info":[{"award-number":["I01BX004033;I01BX001390; IK6BX004477)."]}],"id":[{"id":"10.13039\/501100000938","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Activation of hepatic macrophages represents the critical driving force to promote cholestatic liver injury. Exosomes, as important small extracellular vesicles released by almost all types of cells, contribute to intercellular communication. We previously reported that cholangiocyte-derived exosomal long noncoding RNA (lncRNA) H19 plays a vital role in disrupting bile acid homeostasis in hepatocytes and promoting the activation of hepatic stellate cells (HSCs). Exosomal H19 derived from cholangiocytes was rapidly taken up by Kupffer cells. However, the mechanistic links between exosomal lncRNA H19 and macrophage-driven inflammation in cholestasis remain unclear. Here, we reported that the hepatic H19 level was closely correlated with macrophage activation and hepatic fibrosis in both Mdr2-\/- and bile duct ligation (BDL) cholestatic mouse models, as well as in human primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients. Exosomal H19 significantly induced the expression and secretion of chemokine (C\u2013C motif) ligand 2 (CCL-2) and interleukin 6 (IL-6) in Kupffer cells. H19-enriched exosomes enhanced the activation M1 polarization of Kupffer cells and promoted the recruitment and differentiation of bone marrow-derived macrophages, which were inhibited by a CCL-2 pharmacological inhibitor. In conclusion, Cholangiocyte-derived exosomal H19 played a critical role in macrophage activation, differentiation, and chemotaxis through CCL-2\/CCR-2 signaling pathways, which represent a therapeutic target for cholestatic liver diseases.<\/jats:p>","DOI":"10.3390\/cells9010190","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T04:05:51Z","timestamp":1578888351000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions"],"prefix":"10.3390","volume":"9","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 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"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 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"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 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Anhui University of Chinese Medicine, Hefei 230031, China"}],"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 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.mayocp.2015.03.017","article-title":"The Cholangiopathies","volume":"90","author":"Lazaridis","year":"2015","journal-title":"Mayo. Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jhep.2012.10.011","article-title":"The dynamic biliary epithelia: Molecules, pathways, and disease","volume":"58","author":"Tabibian","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.3748\/wjg.v23.i14.2459","article-title":"Pathogenesis and clinical spectrum of primary sclerosing cholangitis","volume":"23","author":"Gidwaney","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41575-019-0125-y","article-title":"Cholangiocyte pathobiology","volume":"16","author":"Banales","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.29076","article-title":"The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice","volume":"65","author":"Wang","year":"2017","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"30988","DOI":"10.1074\/jbc.M115.668277","article-title":"Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line","volume":"290","author":"Liu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1242\/dev.036061","article-title":"H19 acts as a trans regulator of the imprinted gene network controlling growth in mice","volume":"136","author":"Gabory","year":"2009","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/hep.30698","article-title":"Long non-coding RNA H19 contributes to cholangiocyte proliferation and cholestatic liver fibrosis in biliary atresia","volume":"70","author":"Xiao","year":"2019","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.30662","article-title":"Cholangiocyte-Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis","volume":"70","author":"Liu","year":"2019","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/hep.29145","article-title":"The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice","volume":"66","author":"Li","year":"2017","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7150\/thno.21945","article-title":"Exosome Theranostics: Biology and Translational Medicine","volume":"8","author":"He","year":"2018","journal-title":"Theranostics."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1161\/CIRCRESAHA.117.309419","article-title":"Extracellular Vesicles in Metabolic Syndrome","volume":"120","author":"Martinez","year":"2017","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sato, K., Kennedy, L., Liangpunsakul, S., Kusumanchi, P., Yang, Z., Meng, F., Glaser, S., Francis, H., and Alpini, G. (2019). Intercellular Communication between Hepatic Cells in Liver Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092180"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/hep.29838","article-title":"Cholangiocyte-derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans","volume":"68","author":"Li","year":"2018","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1182\/blood-2007-02-073841","article-title":"Kupffer cell heterogeneity: Functional properties of bone marrow derived and sessile hepatic macrophages","volume":"110","author":"Klein","year":"2007","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/gutjnl-2015-310514","article-title":"Targeting of tumour-infiltrating macrophages via CCL2\/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma","volume":"66","author":"Li","year":"2017","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.jhep.2013.12.025","article-title":"Macrophage heterogeneity in liver injury and fibrosis","volume":"60","author":"Tacke","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev.immunol.26.021607.090326","article-title":"Monocyte-mediated defense against microbial pathogens","volume":"26","author":"Serbina","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1136\/gutjnl-2011-300304","article-title":"Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury","volume":"61","author":"Baeck","year":"2012","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jhep.2018.05.018","article-title":"Macrophages contribute to the pathogenesis of sclerosing cholangitis in mice","volume":"69","author":"Guicciardi","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.22952","article-title":"CCR2 promotes hepatic fibrosis in mice","volume":"50","author":"Seki","year":"2009","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.2353\/ajpath.2009.080632","article-title":"Dual role of CCR2 in the constitution and the resolution of liver fibrosis in mice","volume":"174","author":"Mitchell","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_24","first-page":"e90780","article-title":"Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response","volume":"2","author":"Cai","year":"2017","journal-title":"J.C.I. Insight"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, X., Cao, R., Liu, R., Zhao, R., Huang, Y., Gurley, E.C., Hylemon, P.B., Pandak, W.M., Wang, G., and Zhang, L. (2014). Reduction of the HIV protease inhibitor-induced ER stress and inflammatory response by raltegravir in macrophages. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090856"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00204-016-1697-8","article-title":"Role of AMP-activated protein kinase alpha1 in 17alpha-ethinylestradiol-induced cholestasis in rats","volume":"91","author":"Li","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/hep.27085","article-title":"Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2","volume":"60","author":"Liu","year":"2014","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6166","DOI":"10.4049\/jimmunol.164.12.6166","article-title":"M-1\/M-2 macrophages and the Th1\/Th2 paradigm","volume":"164","author":"Mills","year":"2000","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: Time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000Prime Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.jhep.2019.01.030","article-title":"Extracellular vesicles, the liquid biopsy of the future","volume":"70","author":"Eguchi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Han, W., and Duan, Z. (2019). Roles of exosomes in liver metastases: Novel diagnosis and treatment choices. J. Cell. Physiol.","DOI":"10.1002\/jcp.28785"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/cmi.2015.104","article-title":"Hepatic macrophages in homeostasis and liver diseases: From pathogenesis to novel therapeutic strategies","volume":"13","author":"Ju","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/icb.2017.64","article-title":"Macrophage polarization and function: New prospects for fibrotic disease","volume":"95","author":"Zhou","year":"2017","journal-title":"Immunol. Cell. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cellimm.2017.02.005","article-title":"Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1\/2 phosphatase Dusp6","volume":"314","author":"Carson","year":"2017","journal-title":"Cell. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2007.11.010","article-title":"Mechanisms of cholestasis","volume":"12","author":"Zollner","year":"2008","journal-title":"Clin Liver Dis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1017\/S1462399409000994","article-title":"Cholangiocyte proliferation and liver fibrosis","volume":"11","author":"Glaser","year":"2009","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.bbadis.2017.06.017","article-title":"Mechanisms of cholangiocyte responses to injury","volume":"1864","author":"Sato","year":"2018","journal-title":"Biochim Biophys. Acta Mol. Basis Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.matbio.2017.11.010","article-title":"Inflammation and fibrosis","volume":"68\u201369","author":"Mack","year":"2018","journal-title":"Matrix Biol"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"86","DOI":"10.21037\/atm.2019.01.12","article-title":"Extracellular vesicles in hepatocellular cancer and cholangiocarcinoma","volume":"7","author":"Xie","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1002\/hep.30542","article-title":"Amelioration of Ductular Reaction by Stem Cell Derived Extracellular Vesicles in MDR2 Knockout Mice via Lethal-7 microRNA","volume":"69","author":"McDaniel","year":"2019","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13287-016-0453-6","article-title":"Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure","volume":"8","author":"Chen","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jhep.2015.07.030","article-title":"Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate","volume":"64","author":"Nojima","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15016","DOI":"10.1038\/ncomms15016","article-title":"Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sasaki, R., Kanda, T., Yokosuka, O., Kato, N., Matsuoka, S., and Moriyama, M. (2019). Exosomes and Hepatocellular Carcinoma: From Bench to Bedside. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061406"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.pharmthera.2018.03.009","article-title":"Extracellular vesicles as potential biomarkers for alcohol- and drug-induced liver injury and their therapeutic applications","volume":"187","author":"Cho","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"G990","DOI":"10.1152\/ajpgi.00093.2010","article-title":"Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia","volume":"299","author":"Masyuk","year":"2010","journal-title":"Am. J Physiol. Gastrointest. Liver Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1139\/bcb-2013-0096","article-title":"Chicken biliary exosomes enhance CD4(+)T proliferation and inhibit ALV-J replication in liver","volume":"92","author":"Wang","year":"2014","journal-title":"Biochem. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.jhep.2015.11.020","article-title":"Alcohol stimulates macrophage activation through caspase-dependent hepatocyte derived release of CD40L containing extracellular vesicles","volume":"64","author":"Verma","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1053\/j.gastro.2015.12.037","article-title":"Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes","volume":"150","author":"Hirsova","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/hep.28252","article-title":"Mixed lineage kinase 3 mediates release of C-X-C motif ligand 10-bearing chemotactic extracellular vesicles from lipotoxic hepatocytes","volume":"63","author":"Ibrahim","year":"2016","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.3389\/fimmu.2018.01789","article-title":"Extracellular Vesicles Work as a Functional Inflammatory Mediator Between Vascular Endothelial Cells and Immune Cells","volume":"9","author":"Hosseinkhani","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9991","DOI":"10.1038\/srep09991","article-title":"Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS","volume":"5","author":"Bala","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ebiom.2018.08.054","article-title":"AMSC-derived exosomes alleviate lipopolysaccharide\/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP\/NLRP3 inflammasome activation in macrophages","volume":"36","author":"Liu","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pope, C., Mishra, S., Russell, J., Zhou, Q., and Zhong, X.B. (2017). Targeting H19, an Imprinted Long Non-Coding RNA, in Hepatic Functions and Liver Diseases. Diseases, 5.","DOI":"10.3390\/diseases5010011"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.yjmcc.2019.04.004","article-title":"LncRNA H19 promotes vascular inflammation and abdominal aortic aneurysm formation by functioning as a competing endogenous RNA","volume":"131","author":"Sun","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/15216540600871126","article-title":"Cellular signalling by sphingosine kinase and sphingosine 1-phosphate","volume":"58","author":"Leclercq","year":"2006","journal-title":"IUBMB Life"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.dld.2019.03.020","article-title":"The role of sphingosine kinase 2 in alcoholic liver disease","volume":"51","author":"Kwong","year":"2019","journal-title":"Dig. Liver. Dis."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/1\/190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:04:28Z","timestamp":1760364268000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/1\/190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,11]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["cells9010190"],"URL":"https:\/\/doi.org\/10.3390\/cells9010190","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,11]]}}}