title: Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride-induced mouse liver injury.
abstract: Previous studies have indicated that female animals are more resistant to carbon tetrachloride (CCl(4))-induced liver fibrosis than male animals, and that estradiol (E(2)) treatment can inhibit CCl(4)-induced animal hepatic fibrosis. The underlying mechanism governing these phenomena, however, has not been fully elucidated. Here we reported the role of estrogen-induced miRNA-29 (miR-29) expression in CCl(4)-induced mouse liver injury. Hepatic miR-29 levels were differentially regulated in female and male mice during CCl(4) treatment. Specifically, the levels of miR-29a and miR-29b expression were significantly decreased in the livers of male, but not female, mice following 4 weeks of CCl(4) treatment. The down-regulation of miR-29a and miR-29b in male mouse livers correlated with the early development of liver fibrosis, as indicated by increased expressions of fibrotic markers in male mice relative to female mice. In addition, E(2) was maintained at a higher level in female mice than in male mice. In contrast to TGF-β1 that decreased miR-29a/b expression in murine hepatoma IAR20 cells and normal hepatocytes, E(2) enhanced the expression of miR-29a/b through suppression of the nuclear factor-κB (NF-κB) signal pathway, which negatively regulates miR-29 expression. Furthermore, both E(2) treatment and intravenous injection of the recombinant adenovirus expressing miR-29a/b markedly increased the miR-29a/b level and attenuated the expression of fibrotic markers in mouse livers during CCl(4) treatment, supporting the protective role of E(2)-induced miR-29 in CCl(4)-induced hepatic injury. In conclusion, our results collectively demonstrate that estrogen can inhibit CCl(4)-induced hepatic injury through the induction of hepatic miR-29.
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology (JERC-MBB), State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu 210093, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Linping
authors.initials: L
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Mingcao
authors.initials: M
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhu
authors.forename: Xihan
authors.initials: X
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gu
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis*; D012727:Sex Characteristics; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004967:Estrogens; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D002251:Carbon Tetrachloride