{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:19:17Z","timestamp":1791109157760,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T00:00:00Z","timestamp":1297728000000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic infection of hepatitis C virus (HCV) leads to hepatic fibrosis and subsequently cirrhosis, although the underlying mechanisms have not been established. Previous studies have indicated that the binding of HCV E2 protein and CD81 on the surface of hepatic stellate cells (HSCs) lead to the increased protein level and activity of matrix metallopeptidase (MMP) 2, indicating that E2 may involve in the HCV\u2010induced fibrosis. This study was designed to investigate the involvement of HCV E2 protein in the hepatic fibrogenesis. Results showed that E2 protein may promote the expression levels of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and collagen \u03b1(I). Furthermore, several pro\u2010fibrosis or pro\u2010inflammatory cytokines, including transforming growth factor (TGF)\u2010\u03b21, connective tissue growth factor (CTGF), interleukin (IL)\u20106 and IL\u20101\u03b2, were significantly increased in E2 transfected\u2010HSC cell lines, while the expression of MMP\u20102 are also considerably increased. Moreover, the significant increases of CTGF and TGF\u2010\u03b21 in a stable E2\u2010expressing Huh7 cell line were also observed the same results. Further molecular studies indicated that the impact of E2 protein on collagen production related to higher production of ROS and activated Janus kinase (JAK)1, JAK2 and also enhance the activation of ERK1\/2 and p38, while catalase and inhibitors specific for JAK, ERK1\/2, and p38 abolish E2\u2010enhanced expression of collagen \u03b1(I). Taken together, this study indicated that E2 protein involve in the pathogenesis of HCV\u2010mediated fibrosis via an up\u2010regulation of collagen \u03b1(I) and oxidative stress, which is JAK pathway related. J. Cell. Biochem. 112: 233\u2013243, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22926","type":"journal-article","created":{"date-parts":[[2010,11,10]],"date-time":"2010-11-10T16:46:20Z","timestamp":1289407580000},"page":"233-243","source":"Crossref","is-referenced-by-count":59,"title":["Hepatitis C virus E2 protein induce reactive oxygen species (ROS)\u2010related fibrogenesis in the HSC\u2010T6 hepatic stellate cell line"],"prefix":"10.1002","volume":"112","author":[{"given":"Hsieh","family":"Ming\u2010Ju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsieh","family":"Yih\u2010Shou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tzy\u2010Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiou","family":"Hui\u2010Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.1999.tb00038.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.11.018"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2741\/beljaars","article-title":"Targeting hepatic stellate cells for cell\u2010specific treatment of liver fibrosis","volume":"7","author":"Beljaars L","year":"2002","journal-title":"Front Biosci"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.037531"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17552"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.30204"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-858989"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201941200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00128.2002"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308351200"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20622"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.07.027"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17580"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.3.F495"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.04.118"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014471213371"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5332.1630"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.19.11039"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203481"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00459-07"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2247"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310118"},{"key":"e_1_2_6_24_1","first-page":"5","article-title":"Hepatic fibrogenesis: The puzzle of interacting cells, fibrogenic cytokines, regulatory loops, and extracellular matrix molecules","volume":"30","author":"Gressner AM","year":"1992","journal-title":"Z Gastroenterol"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2006.04.002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210485200"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(96)00118-5"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17557"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00886.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S1665-2681(19)32127-1","article-title":"Liver fibrosis and inflammation. 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