title: Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways.
abstract: Fibroblast growth factor 21 (FGF-21) is a secreted protein, which has anti-diabetic and lipocaic effects, but its ability to protect against hepatic fibrosis has not been studied. In this study, we investigated the ability of FGF-21 to attenuate dimethylnitrosamine (DMN)-induced hepatic fibrogenesis in mice and the mechanism of its action. Hepatic fibrosis was induced by injection of DMN, FGF-21 was administered to the mice once daily in association with DMN injection till the end of the experiment. Histopathological examination, tissue 4-hydroxyproline content and expressions of smooth muscle α-actin (α-SMA) and collagen I were measured to assess hepatic fibrosis. Ethanol/PDGF-BB-activated hepatic stellate cells (HSCs) were used to understand the mechanisms of FGF-21 inhibited hepatic fibrogenesis. Results showed that FGF-21 treatment attenuated hepatic fibrogenesis and was associated with a significant decrease in intrahepatic fibrogenesis, 4-hydroxyproline accumulation, α-SMA expression and collagen I deposition. FGF-21 treatment inhibited the activation of HSCs via down-regulating the expression of TGF-β, NF-κB nuclear translocation, phosphorylation levels of smad2/3 and IκBα. Besides, FGF-21 treatment caused activated HSC apoptosis with increasing expression of Caspase-3, and decreased the ratio of Bcl-2 to Bax. In conclusion, FGF-21 attenuates hepatic fibrogenesis and inhibits the activation of HSC warranting the use of FGF-21 as a potential therapeutic agent in the treatment of hepatic fibrosis.
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Song
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Zhihang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Yongbi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China. Electronic address: renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity; D015536:Down-Regulation; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C494827:Bax protein, mouse; D024042:Collagen Type I; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D051028:bcl-2-Associated X Protein; C414620:fibroblast growth factor 21; C052617:Bcl2 protein, mouse; D005346:Fibroblast Growth Factors; C505409:Casp3 protein, mouse; D053148:Caspase 3; D004128:Dimethylnitrosamine; D006909:Hydroxyproline
keywords: Fibroblast growth factor 21; Hepatic fibrogenesis; Hepatic stellate cells; NF-κB; TGF-β