{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T09:34:17Z","timestamp":1793266457065,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T00:00:00Z","timestamp":1519257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400630"],"award-info":[{"award-number":["81400630"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>The aim of this study is to explore the roles of estrogen receptor (ER) subtypes and corresponding agonists\/antagonists on the development of cirrhosis and activation and proliferation of hepatic stellate cells (HSCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced cirrhotic ovariectomized rats were administered non\u2010selective ER agonist (\u03b2\u2010estradiol, E2), ER selective agonists (ER\u03b1 agonist, propylpyrazoletriol; ER\u03b2 agonist, diarylpropionitrile [DPN]; and G\u2010protein\u2010coupled ER [GPER] agonist, G1), or E2\u00a0+\u00a0ER selective antagonists (ER\u03b1 antagonist, MPP; ER\u03b2 antagonist, PHTPP; and GPER antagonist, G15) for 12\u00a0weeks. The expression of the three ER subtypes in livers and HSCs and the effects of the drugs on hepatic fibrosis, isolated HSCs, and uteri were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Selective ER agonists\/antagonists had various effects on CCl<jats:sub>4<\/jats:sub>\u2010induced cirrhosis. The cirrhotic rats in the CCl<jats:sub>4<\/jats:sub>\u00a0+\u00a0E2, CCl<jats:sub>4<\/jats:sub>\u00a0+\u00a0DPN, CCl<jats:sub>4<\/jats:sub>\u00a0+\u00a0E2\u00a0+\u00a0MPP, and CCl<jats:sub>4<\/jats:sub>\u00a0+\u00a0E2\u00a0+\u00a0G15 groups presented reduced fibrosis scores, compared with those in the CCl<jats:sub>4<\/jats:sub> group. The cirrhotic rats in the E2\u00a0+\u00a0PHTPP group presented increased fibrosis scores that similar to those in the CCl<jats:sub>4<\/jats:sub> group. The ovariectomized rats had enlarged uteri with increased uterus indexes after E2 administration; however, the proliferative effects of E2 were partially blocked by MPP or G15, but not PHTPP. In the <jats:italic>in vitro<\/jats:italic> study, DPN attenuated the transformation of quiescent HSCs to activated phenotype, suppressed collagen I, and \u03b1\u2010smooth muscle actin expression. DPN also suppressed platelet\u2010derived growth factor\u2010induced proliferation in cultured HSCs, which was reversed by PHTPP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The antifibrogenic effects of estrogen were mediated by ER\u03b2 but not ER\u03b1 or GPER. The ER\u03b2 selective agonist exerted a fibrosuppressive effect by inhibiting the activation and proliferation of HSCs, but did not induce uterine hyperplasia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.13976","type":"journal-article","created":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T04:02:52Z","timestamp":1504843372000},"page":"747-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Estrogen receptor <b>\u03b2<\/b> selective agonist ameliorates liver cirrhosis in rats by inhibiting the activation and proliferation of hepatic stellate cells"],"prefix":"10.1111","volume":"33","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Gang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u2010Hua","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0676.2003.00811.x"},{"key":"e_1_2_5_3_1","first-page":"115","article-title":"\u201cImmune activation, aging and gender\u201d and progression of liver disease","volume":"82","author":"Nasta P","year":"2011","journal-title":"Acta Biomed"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00032.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i32.4295"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1413-86702007000300014"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2005.00082.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2003.08.004"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i9.1315"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5479"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-010-9263-9"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20463"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-010-9554-8"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0486"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.122"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.101931"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i18.4484"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.08.017"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v8.i5.883"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.44.1.127"},{"key":"e_1_2_5_21_1","first-page":"1261","article-title":"Localization of androgen and estrogen receptors in rat and primate tissues","volume":"15","author":"Pelletier G","year":"2000","journal-title":"Histol. Histopathol."},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(02)00102-8"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i2.250"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.06.044"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.20184"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.168"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp187"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.K09E-332"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R110.180109"},{"key":"e_1_2_5_30_1","doi-asserted-by":"crossref","DOI":"10.1621\/nrs.06003","article-title":"Estrogen receptor beta: an overview and update","volume":"6","author":"Zhao C","year":"2008","journal-title":"Nucl. Recept. Signal."},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0459"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0010"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm010254a"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1299595"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.00800"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.261"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3505"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjgh.13976","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.13976","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T16:21:03Z","timestamp":1695486063000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.13976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,22]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/jgh.13976"],"URL":"https:\/\/doi.org\/10.1111\/jgh.13976","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,22]]},"assertion":[{"value":"2017-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}