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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 asmore » a potential therapeutic agent in the treatment of hepatic fibrosis. - Highlights: • Fibroblast growth factor 21 attenuates hepatic fibrogenesis. • Fibroblast growth factor 21 attenuates hepatic fibrogenesis via TGF-β/smad2/3 signaling pathways. • Fibroblast growth factor 21 attenuates hepatic fibrogenesis via NF-κB signaling pathways.« less

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
OSTI Identifier:
22687867
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 290; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; APOPTOSIS; BORON CHLORIDES; COLLAGEN; ETHANOL; FIBROBLASTS; FIBROSIS; GROWTH FACTORS; HYDROXYPROLINE; INJECTION; LIVER; MICE; PHOSPHORYLATION; PLANT GROWTH

Citation Formats

Xu, Pengfei, Zhang, Yingjie, Liu, Yunye, Yuan, Qingyan, Song, Liying, Liu, Mingyao, Liu, Zhihang, Yang, Yongbi, Li, Junyan, Li, Deshan, E-mail: deshanli@163.com, and Ren, Guiping, E-mail: renguiping@126.com. Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways. United States: N. p., 2016. Web. doi:10.1016/J.TAAP.2015.11.012.
Xu, Pengfei, Zhang, Yingjie, Liu, Yunye, Yuan, Qingyan, Song, Liying, Liu, Mingyao, Liu, Zhihang, Yang, Yongbi, Li, Junyan, Li, Deshan, E-mail: deshanli@163.com, & Ren, Guiping, E-mail: renguiping@126.com. Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways. United States. doi:10.1016/J.TAAP.2015.11.012.
Xu, Pengfei, Zhang, Yingjie, Liu, Yunye, Yuan, Qingyan, Song, Liying, Liu, Mingyao, Liu, Zhihang, Yang, Yongbi, Li, Junyan, Li, Deshan, E-mail: deshanli@163.com, and Ren, Guiping, E-mail: renguiping@126.com. Fri . "Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways". United States. doi:10.1016/J.TAAP.2015.11.012.
@article{osti_22687867,
title = {Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways},
author = {Xu, Pengfei and Zhang, Yingjie and Liu, Yunye and Yuan, Qingyan and Song, Liying and Liu, Mingyao and Liu, Zhihang and Yang, Yongbi and Li, Junyan and Li, Deshan, E-mail: deshanli@163.com and Ren, Guiping, E-mail: renguiping@126.com},
abstractNote = {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. - Highlights: • Fibroblast growth factor 21 attenuates hepatic fibrogenesis. • Fibroblast growth factor 21 attenuates hepatic fibrogenesis via TGF-β/smad2/3 signaling pathways. • Fibroblast growth factor 21 attenuates hepatic fibrogenesis via NF-κB signaling pathways.},
doi = {10.1016/J.TAAP.2015.11.012},
journal = {Toxicology and Applied Pharmacology},
number = ,
volume = 290,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 2016},
month = {Fri Jan 01 00:00:00 EST 2016}
}