{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:43:39Z","timestamp":1791834219025,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20190909"],"award-info":[{"award-number":["BK20190909"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound extracted from\n                    <jats:italic>Mangifera indica<\/jats:italic>\n                    L, has been reported to attenuate liver injury. This study aimed to investigate the mechanisms underlying HSP27 inhibition and the anti\u2010fibrotic effect of MAN in liver fibrosis. Our results revealed that the expression of HSP27 was remarkably increased in the liver tissues of patients with liver cirrhosis and CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced fibrotic rats. However, HSP27 shRNA treatment significantly alleviated fibrosis. Furthermore, MAN was found to inhibit CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010 and TGF\u2010\u03b21\u2010induced liver fibrosis and reduced hepatocyte EMT. More importantly, MAN decreased HSP27 expression to suppress the JAK2\/STAT3 pathway, and subsequently blocked TGF\u2010\u03b21\/Smad signaling, which were consistent with its protection against CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced EMT and liver fibrosis. Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2\/STAT3 signaling and TGF\u2010\u03b21\/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.7549","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T07:05:13Z","timestamp":1656745513000},"page":"4167-4182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Mangiferin prevents hepatocyte epithelial\u2010mesenchymal transition in liver fibrosis via targeting\n                    <scp>HSP27<\/scp>\n                    \u2010mediated\n                    <scp>JAK2<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    and\n                    <scp>TGF<\/scp>\n                    \u2010\u03b21\/Smad pathway"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-0976","authenticated-orcid":false,"given":"Xiao\u2010ling","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Pharmacy Nantong University  Nantong PR China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Translational Medicine, Medical College, Yangzhou University  Yangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0723-143X","authenticated-orcid":false,"given":"Xiao\u2010qun","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Translational Medicine, Medical College, Yangzhou University  Yangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Nantong University  Nantong PR China"},{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08557-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5957"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16092-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.28457"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.153055"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1519197113"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-15-0952"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006927"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf100249s"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092592"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0080-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1309"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029719"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27117"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2741\/a812"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.773515"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a003139"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.138"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci39104"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0556-9"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9840"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1308-8"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-18-3900"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2015.107"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101600"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0086-3"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6842"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2003.10.005"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9fo00153k"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2586706"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i23.2889"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.capr-11-0121"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22397"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209281"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.12.006"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.09.002"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2019.04.015"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1631-3"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.07.031"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26414"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03627-9"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2018.11.004"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14573"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3182789b2b"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26475"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm5010009"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13065"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90240.2008"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2014.12.017"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2813"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1432"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-220053"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-018-0194-4"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00204-4"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1693"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2429-9"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.12.019"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.7549","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T06:17:22Z","timestamp":1692685042000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.7549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,2]]},"references-count":58,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/ptr.7549"],"URL":"https:\/\/doi.org\/10.1002\/ptr.7549","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,2]]},"assertion":[{"value":"2021-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}