title: Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis.
abstract: Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis, which is a pathological process characterized by extracellular matrix accumulation. NR4A2 is a nuclear receptor belonging to the NR4A subfamily and vital in regulating cell growth, metabolism, inflammation and other biological functions. However, its role in HSCs is unclear. We analyzed NR4A2 expression in fibrotic liver and stimulated HSCs compared with control group and studied the influence on cell proliferation, cell cycle, cell apoptosis and MAPK pathway after NR4A2 knockdown. NR4A2 expression was examined by real-time polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence analyses. NR4A2 expression was significantly lower in fibrotic liver tissues and PDGF BB or TGF-β stimulated HSCs compared with control group. After NR4A2 knockdown α-smooth muscle actin and Col1 expression increased. In addition, NR4A2 silencing led to the promotion of cell proliferation, increase of cell percentage in S phase and reduced phosphorylation of ERK1/2, P38 and JNK in HSCs. These results indicate that NR4A2 can inhibit HSC proliferation through MAPK pathway and decrease extracellular matrix in liver fibrogenesis. NR4A2 may be a promising therapeutic target for liver fibrosis.
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China ; Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Pengguo
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , 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 , 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 , 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 , 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 , Shanghai , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , 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 , Shanghai , China ; Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Guo
keywords: Fibrosis; Hepatic stellate cell; MAPK; NR4A2; Proliferation