{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T03:25:24Z","timestamp":1786764324928,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T00:00:00Z","timestamp":1534464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["H2016098"],"award-info":[{"award-number":["H2016098"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>The aim of this study was to evaluate the hypothesis that emodin inhibits extracellular matrix (ECM)\u2010related gene expression in activated hepatic stellate cells (HSCs) by blocking canonical or\/and noncanonical components of transforming growth factor \u03b21 (TGF\u03b21) intracellular signaling. Here, we demonstrate that emodin suppressed the gene expression of HSCs activation markers type I collagen, fibronectin, and \u03b1\u2010smooth muscle actin, as well as HSCs proliferation. Mechanistically, emodin suppresses TGF\u03b21, TGF\u03b2 receptor II, TGF\u03b2 receptor I, and Smad4 gene expression, as well as Smad luciferase activity. Simultaneously, emodin reduced p38 mitogen\u2010activated protein kinase (p38<jats:sup>MAPK<\/jats:sup>) activity but not c\u2010Jun N\u2010terminal kinases and extracellular signal\u2010regulated kinases 1 and 2 phosphorylation in HSC\u2010T6 cells. Interestingly, deprivation of TGF\u03b2 using a neutralizing antibody abolished emodin\u2010mediated inhibitions of the both Smad transcriptional activity and p38<jats:sup>MAPK<\/jats:sup> phosphorylation. Furthermore, emodin\u2010mediated inhibition of HSCs activation could be partially blocked by PD98059 inhibition of p38<jats:sup>MAPK<\/jats:sup> or short hairpin RNA\u2010imposed knockdown of Smad4. Conversely, simultaneous inhibition of Smad4 and p38<jats:sup>MAPK<\/jats:sup> pathways completely reverses the effects of emodin, suggesting that Smad and p38<jats:sup>MAPK<\/jats:sup> locate downstream of TGF\u03b21 and regulate collagen genes expression in HSCs. Collectively, these data suggest that emodin is a promising candidate for the treatment of hepatic fibrosis.<\/jats:p>","DOI":"10.1002\/ptr.6182","type":"journal-article","created":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T09:57:16Z","timestamp":1534499836000},"page":"2436-2446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Emodin suppresses activation of hepatic stellate cells through <scp>p38<\/scp> mitogen\u2010activated protein kinase and <scp>Smad<\/scp> signaling pathways in vitro"],"prefix":"10.1002","volume":"32","author":[{"given":"Xiaoli","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Qiqihar Medical University  Qiqihar China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengu","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Institute of Medicine Qiqihar Medical University  Qiqihar China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-2039","authenticated-orcid":false,"given":"Miaoxian","family":"Dong","sequence":"additional","affiliation":[{"name":"The Institute of Medicine Qiqihar Medical University  Qiqihar China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-011-0898-y"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-016-9758-x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17558"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2011.03.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2014.09.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-015-1525-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2008.05048.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.05.002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10790"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.05.027"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2017.1290233"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.4753"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5631"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2016.1251309"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.10.015"},{"key":"e_1_2_8_17_1","first-page":"29","article-title":"Role of LncRNA\u2010activated by transforming growth factor beta in the progression of hepatitis C virus\u2010related liver fibrosis","volume":"22","author":"Fu N.","year":"2016","journal-title":"Discovery Medicine"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2016.06.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12636"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.02.038"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.06.001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.09.039"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000445269"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2005.pto_96614.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4158"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.12.004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.01.008"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000512"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-016-9631-7"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i41.11552"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312431"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M314048200"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.773085"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000456281"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0248PS"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409381200"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells3040981"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415627681"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.10.016"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2012.105"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5838"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2012.07.006"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.03.009"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X12500371"},{"key":"e_1_2_8_45_1","first-page":"505","article-title":"Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1\/2 pathways in TGF\u2010\u03b21\u2010stimulated NRK\u201049F cells","volume":"4","author":"Zhu B.","year":"2011","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2016.03.013"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv111"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.6182","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.6182","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T16:25:48Z","timestamp":1694795148000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.6182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,17]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/ptr.6182"],"URL":"https:\/\/doi.org\/10.1002\/ptr.6182","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,17]]},"assertion":[{"value":"2018-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}