{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:38:53Z","timestamp":1783593533409,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T00:00:00Z","timestamp":1615680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["BX001721"],"award-info":[{"award-number":["BX001721"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA017226"],"award-info":[{"award-number":["AA017226"]}],"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":["AA015407"],"award-info":[{"award-number":["AA015407"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Hepato Biliary Pancreat"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Purpose<\/jats:title><jats:p>Heavy alcohol drinking is associated with pancreatitis. Pancreatitis is initiated by the damage to the pancreatic acinar cells. The endoplasmic reticulum (ER) stress has been shown to play an important role in alcohol\u2010induced pancreatic damage. Mesencephalic astrocyte\u2010derived neurotrophic factor (MANF) is an ER stress\u2010inducible protein. The aim of the study was to determine whether MANF can ameliorate alcohol\u2010induced ER stress and cellular damages to pancreatic acinar cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Alcohol\u2010induced damage to mouse pancreatic 266\u20106 acinar cells was determined by MTT and flow cytometry. MANF expression was downregulated by MANF siRNA using the Neon Transfection System. The overexpression of MANF was performed by the infection with the adenoviral vector carrying mouse MANF gene. The expression of ER stress markers was determined by immunoblotting and immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol caused ER stress, oxidative stress and induced apoptosis of 266\u20106 acinar cells. Recombinant human MANF alleviated alcohol\u2010induced ER stress and cell death by inhibiting IRE1\u2010caspase 12\u2010caspase 3 apoptotic pathway. Overexpression of mouse MANF also protected cells against alcohol\u2010induced apoptosis. In contrast, inhibiting MANF by siRNA exacerbated alcohol\u2010induced cellular damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MANF was protective against alcohol\u2010induced ER stress and cellular injury in pancreatic acinar cells. The findings suggest a potential therapeutic value of MANF for alcoholic pancreatitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jhbp.928","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T02:12:30Z","timestamp":1614564750000},"page":"883-892","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["MANF protects pancreatic acinar cells against alcohol\u2010induced endoplasmic reticulum stress and cellular injury"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1869-4106","authenticated-orcid":false,"given":"Huaxun","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology Key Laboratory of Anti\u2010inflammatory and Immune Medicine Ministry of Education Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Iowa Carver College of Medicine Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Iowa Carver College of Medicine Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell and Development Biology Vanderbilt University School of Medicine Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences University of Kentucky College of Medicine Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences University of Kentucky College of Medicine Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences University of Kentucky College of Medicine Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology Key Laboratory of Anti\u2010inflammatory and Immune Medicine Ministry of Education Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Iowa Carver College of Medicine Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,14]]},"reference":[{"issue":"4","key":"e_1_2_7_2_1","first-page":"387","article-title":"Alcohol as a risk factor for pancreatitis. A systematic review and meta\u2010analysis","volume":"10","author":"Irving HM","year":"2009","journal-title":"JOP"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.08.017"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.36"},{"key":"e_1_2_7_5_1","first-page":"271","volume-title":"The exocrine pancreas","author":"Pandol SJ","year":"2010"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033886"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.08.036"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:20:2:173"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01629"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db17-1149"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60649-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2015.01.011"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2004.tb00330.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026619666190521093049"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000453164"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2013.06.010"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1299.032"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13078"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1360-1385(02)02312-9"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2010.01409.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2522-3_15"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2016.05.007"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.5.997"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.11.038"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.06.016"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.06.042"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.10.008"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes4030306"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9180"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08133"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.06.016"}],"container-title":["Journal of Hepato-Biliary-Pancreatic Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jhbp.928","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jhbp.928","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jhbp.928","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T08:15:18Z","timestamp":1693210518000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jhbp.928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,14]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/jhbp.928"],"URL":"https:\/\/doi.org\/10.1002\/jhbp.928","archive":["Portico"],"relation":{},"ISSN":["1868-6974","1868-6982"],"issn-type":[{"value":"1868-6974","type":"print"},{"value":"1868-6982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,14]]},"assertion":[{"value":"2020-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}