title: Adenovirus-mediated expression of orphan nuclear receptor NR4A2 targeting hepatic stellate cell attenuates liver fibrosis in rats.
abstract: Liver fibrosis is a wound-healing response characterized with the accumulation of extracellular matrix (ECM). And hepatic stellate cells (HSCs) are the principal cell source of ECM. NR4A2 (Nurr1) is a member of orphan nuclear receptor NR4A family and acts as transcription factor. It participates in regulating cell differentiation, proliferation and apoptosis. We previously demonstrated that NR4A2 expression in fibrotic liver reduced significantly compared with normal liver and NR4A2 knockout in HSCs promoted ECM production. In the present study we explored the role of NR4A2 on liver fibrosis. Studies in cultured HSCs demonstrated that NR4A2 over-expression suppressed the activation of HSCs, such as ECM production and invasion ability. Moreover cell cycle was arrested, cell apoptosis was promoted and cell signaling pathway was influenced. Adenovirus-mediated delivery of NR4A2 in rats ameliorated significantly dimethylnitrosamine (DMN) induced liver fibrosis. The In vivo experiments produced results consistent with in vitro experiments. Taken together these results demonstrate NR4A2 enhancement attenuates liver fibrosis via suppressing the activation of HSCs and NR4A2 may be an ideal target for anti-fibrotic therapy.
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.|Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Gastroenterology, Jiangxi Provincial People's Hospital, 92 Aiguo Road, Nanchang, Jiangxi, China.
authors.forename: Pengguo
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Jinlu
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.
authors.forename: Run
authors.initials: R
authors.lastname: Gan
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, China.|Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Guo
mesh_terms: D021581:Active Transport, Cell Nucleus; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004128:Dimethylnitrosamine / Q000009:adverse effects; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D014161:Transduction, Genetic
chemical_list: C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004128:Dimethylnitrosamine