{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:33:52Z","timestamp":1777451632363,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST108\u20102314\u2010B\u2010110\u2010003\u2010MY2"],"award-info":[{"award-number":["MOST108\u20102314\u2010B\u2010110\u2010003\u2010MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CMRPG8D0642"],"award-info":[{"award-number":["CMRPG8D0642"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CMRPG8G0031"],"award-info":[{"award-number":["CMRPG8G0031"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CLRPG8I0032"],"award-info":[{"award-number":["CLRPG8I0032"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["VGHKS100\u2010025"],"award-info":[{"award-number":["VGHKS100\u2010025"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["VGHKS109\u2010004"],"award-info":[{"award-number":["VGHKS109\u2010004"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015045","name":"Kaohsiung Armed Forces General Hospital","doi-asserted-by":"publisher","award":["108\u201036"],"award-info":[{"award-number":["108\u201036"]}],"id":[{"id":"10.13039\/501100015045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015045","name":"Kaohsiung Armed Forces General Hospital","doi-asserted-by":"publisher","award":["109\u201007"],"award-info":[{"award-number":["109\u201007"]}],"id":[{"id":"10.13039\/501100015045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma\u2010derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin A (ConA)\u2010induced hepatitis model. In cultured hepatocytes, ConA treatment\u2010elicited HDGF upregulation at transcriptional level and promoted HDGF secretion while reducing intracellular HDGF protein level and cellular viability. Similarly, mice receiving ConA administration exhibited reduced hepatic HDGF expression and elevated circulating HDGF level, which was positively correlated with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. By using HDGF knockout (KO) mice, it was found the ConA\u2010evoked cell death was prominently alleviated in KO compared with control. Besides, it was delineated HDGF ablation conferred protection by suppressing the ConA\u2010induced neutrophils recruitment in livers. Above all, the ConA\u2010mediated activation of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1)\/interleukin\u20101\u03b2 (IL\u20101\u03b2)\/interleukin\u20106 (IL\u20106)\/cyclooxygenase\u20102 (COX\u20102) inflammatory signaling was significantly abrogated in KO mice. Treatment with recombinant HDGF (rHDGF) dose\u2010dependently stimulated the expression of TNF\u2010\u03b1\/IL\u20101\u03b2\/IL\u20106\/COX\u20102 in hepatocytes, further supporting the pro\u2010inflammatory function of HDGF. Finally, application of HDGF antibody not only attenuated the ConA\u2010mediated inflammatory cascade in hepatocytes, but also ameliorated the ConA\u2010induced hepatic necrosis and AST elevation in mice. In summary, HDGF participates in ConA\u2010induced hepatitis via neutrophils recruitment and may constitute a therapeutic target for acute hepatitis.<\/jats:p>","DOI":"10.1096\/fj.202000511rr","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T02:32:18Z","timestamp":1602815538000},"page":"16163-16178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hepatoma\u2010derived growth factor participates in concanavalin A\u2010induced hepatitis"],"prefix":"10.1096","volume":"34","author":[{"given":"E\u2010Ming","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences National Sun Yat\u2010sen University Kaohsiung Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung\u2010Hui","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Hepato\u2010Gastroenterology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao\u2010Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Biobank and Tissue Bank Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan"},{"name":"Department of Pathology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Chen","family":"Chang","sequence":"additional","affiliation":[{"name":"Doctoral Degree Program in Marine Biotechnology National Sun Yat\u2010sen University and Academia Sinica Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih\u2010Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences National Sun Yat\u2010sen University Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih\u2010Tsung","family":"Huang","sequence":"additional","affiliation":[{"name":"Doctoral Degree Program in Marine Biotechnology National Sun Yat\u2010sen University and Academia Sinica Kaohsiung Taiwan"},{"name":"LabTurbo Biotech Corporation Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Ching","family":"Wu","sequence":"additional","affiliation":[{"name":"Biobank and Tissue Bank Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan"},{"name":"Department of Pathology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Ling","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Nephrology Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoi\u2010Hung","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Conde S. Janu\u00e1rio Hospital Macau China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biological Science &amp; Technology I\u2010Shou University Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Bin","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences National Sun Yat\u2010sen University Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei\u2010Lang","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010Hong","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources Asia\u2010Pacific Ocean Research Center, National Sun Yat\u2010sen University Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jui\u2010Chu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chou\u2010Yuan","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Kaohsiung Armed Forces General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Lun","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian\u2010Huei","family":"Chu","sequence":"additional","affiliation":[{"name":"Biobank and Tissue Bank Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan"},{"name":"Department of Medical Research Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Hong","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Sun Yat\u2010sen University Kaohsiung Taiwan"},{"name":"Doctoral Degree Program in Marine Biotechnology National Sun Yat\u2010sen University and Academia Sinica Kaohsiung Taiwan"},{"name":"Institute of Biomedical Sciences National Sun Yat\u2010sen University Kaohsiung Taiwan"},{"name":"Center for Neuroscience National Sun Yat\u2010sen University Kaohsiung Taiwan"},{"name":"Regenerative Medicine and Cell Therapy Research Center Kaohsiung Medical University Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30991"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.002"},{"key":"e_1_2_9_4_1","first-page":"117","article-title":"The de ritis ratio: the test of time","volume":"34","author":"Botros M","year":"2013","journal-title":"Clin Biochem Rev"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115836"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215572841"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.1.45"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.11.009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/189785"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.57"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00758"},{"key":"e_1_2_9_12_1","first-page":"63","article-title":"Tetracycline derivative minocycline inhibits autophagy and inflammation in concanavalin\u2010a\u2010activated human hepatoma cells","volume":"8","author":"Desjarlais M","year":"2014","journal-title":"Gene Regul Syst Bio"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(89)90361-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2687"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11653"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.04.031"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30795"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.10.002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3608"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0886-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-011-0733-z"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722056115"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21589"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67484"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im0320s110"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1487"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1745"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500153"},{"key":"e_1_2_9_29_1","first-page":"L238","article-title":"TNF\u2010alpha\u2010induced transendothelial neutrophil migration is IL\u20108 dependent","volume":"266","author":"Smart SJ","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-007-9047-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.3.2189"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812782106"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-015-1200-7"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306164"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr200573b"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.242.101"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21509"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2011.01408.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)90482-6"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.9374"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2781"},{"key":"e_1_2_9_42_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.urolonc.2016.05.027","article-title":"Hepatoma\u2010derived growth factor: a survival\u2010related protein in prostate oncogenesis and a potential target for vitamin K2","volume":"34","author":"Shetty A","year":"2016","journal-title":"Urol Oncol"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.12.001"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02014"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2012.05.006"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/10338"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000511RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202000511RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000511RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:45:20Z","timestamp":1761673520000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202000511RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,15]]},"references-count":45,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1096\/fj.202000511RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202000511rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,15]]},"assertion":[{"value":"2020-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}