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Interestingly, endoplasmic reticulum (ER) stress is closely associated with liver\ninjury and the activation of NF-\u03baB signaling.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>Here, we investigated the impact of ER stress on MRP2 expression and the\nfunctional involvement of MRP2 in acute liver injury.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>ER stress, MRP2 expression, and hepatocyte injury were analyzed in a\ncarbon tetrachloride (CCl4)-induced mouse model of acute liver injury and in a\nthapsigargin (TG)-induced model of ER stress.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>CCl4 and TG induced significant ER stress, MRP2 protein expression and NF-\n\u03baB activation in mice and LO2 cells (P&lt;0.05). Pretreatment with ER stress inhibitor 4-\nphenyl butyric acid (PBA) significantly mitigated CCl4 and TG-induced ER stress and\nMRP2 protein expression (P&lt;0.05). Moreover, pretreatment with pyrrolidine\ndithiocarbamic acid (PDTC; NF-\u03baB inhibitor) significantly inhibited CCl4-induced NF-\u03baB\nactivation and reduced MRP2 protein expression (1\u00b10.097 vs. 0.623\u00b10.054; P&lt;0.05).\nFurthermore, hepatic downregulation of MRP2 expression significantly increased CCl4-\ninduced ER stress, apoptosis, and liver injury.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>ER stress enhances intrahepatic MRP2 protein expression by activating\nNF-\u03baB. This increase in MRP2 expression mitigates ER stress and acute liver injury.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1566524020666200124102411","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T15:02:30Z","timestamp":1579878150000},"page":"548-557","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Endoplasmic Reticulum Stress Increases Multidrug-resistance Protein 2 Expression and Mitigates Acute Liver Injury"],"prefix":"10.2174","volume":"20","author":[{"given":"Wen-Ge","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Zhen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Wan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Huai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1002\/jhbp.400","volume":"23","author":"Furuyama T.","year":"2016","unstructured":"Furuyama T.; Kudo A.; Matsumura S.; Preoperative direct bilirubin to prothrombin time ratio index to prevent liver failure after minor hepatectomy. 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