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Mice received\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n 5\u00a0\n \u03bc<\/jats:italic>\n L\/g body wt i.p. twice a week for 4\u00a0wk or 6\u00a0wk. Melatonin was given at 5 or 10\u00a0mg\/kg\/day i.p, beginning 2\u00a0wk after the start of\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n administration. Treatment with\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n resulted in fibrosis evidenced by the staining of\n \u03b1<\/jats:italic>\n \u2010smooth muscle actin (\n \u03b1<\/jats:italic>\n \u2010\n SMA<\/jats:styled-content>\n )\u2010positive cells.\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n induced an autophagic response measured as the presence of autophagic vesicles, protein 1 light chain 3 (\n LC<\/jats:styled-content>\n 3) staining, conversion of\n LC<\/jats:styled-content>\n 3\u2010I to autophagosome\u2010associated\n LC<\/jats:styled-content>\n 3\u2010\n II<\/jats:styled-content>\n , changes in expression of beclin\u20101,\n UV<\/jats:styled-content>\n radiation resistance\u2010associated gene (\n UVRAG<\/jats:styled-content>\n ), ubiquitin\u2010like autophagy\u2010related (Atg5), Atg12, Atg16L1, sequestosome 1 (p62\/\n SQSTM<\/jats:styled-content>\n 1), and lysosome\u2010associated membrane protein (\n LAMP<\/jats:styled-content>\n )\u20102, and increased phosphorylation of the mammalian target of rapamycin (\n mTOR<\/jats:styled-content>\n ). There was an increase in the expression of the\n ER<\/jats:styled-content>\n stress chaperones\n CCAAT<\/jats:styled-content>\n \/enhancer\u2010binding protein homologous protein (\n CHOP<\/jats:styled-content>\n ), immunoglobulin\u2010heavy\u2010chain\u2010binding protein (BiP\/\n GRP<\/jats:styled-content>\n 78), and 94\u2010\n kD<\/jats:styled-content>\n a glucose\u2010regulated protein (\n GRP<\/jats:styled-content>\n 94), and in the\n mRNA<\/jats:styled-content>\n levels of pancreatic\n ER<\/jats:styled-content>\n kinase (\n PERK<\/jats:styled-content>\n ), activating transcription factor 6 (\n ATF<\/jats:styled-content>\n 6),\n ATF<\/jats:styled-content>\n 4, inositol\u2010requiring enzyme 1 (\n IRE<\/jats:styled-content>\n 1), and spliced X\u2010box\u2010binding protein\u20101 (\n XBP<\/jats:styled-content>\n 1). Phospho\u2010\n IRE<\/jats:styled-content>\n 1,\n ATF<\/jats:styled-content>\n 6, and phospho\u2010\n PERK<\/jats:styled-content>\n protein concentration also increased significantly. Immunohistochemical staining of\n \u03b1<\/jats:italic>\n \u2010\n SMA<\/jats:styled-content>\n indicated an abrogation of hepatic stellate cells activation by melatonin. Furthermore, treatment with the indole resulted in significant inhibition of the autophagic flux and the unfolded protein response. Findings from this study give new insight into molecular pathways accounting for the protective effect of melatonin in fibrogenesis.\n <\/jats:p>","DOI":"10.1111\/jpi.12247","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T22:13:52Z","timestamp":1431123232000},"page":"151-162","source":"Crossref","is-referenced-by-count":91,"title":["RETRACTED: Melatonin inhibits autophagy and endoplasmic reticulum stress in mice with carbon tetrachloride\u2010induced fibrosis"],"prefix":"10.1111","volume":"59","author":[{"given":"Beatriz","family":"San\u2010Miguel","sequence":"first","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Crespo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Le\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana I.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara","family":"Gonz\u00e1lez\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan J.","family":"Ortiz de Urbina","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda J.","family":"Tu\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n 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