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dc.contributor.authorChen, Qiang
dc.contributor.author陈强
dc.contributor.authorJiang, Yuan
dc.contributor.authorAn, Yuan
dc.contributor.authorZhao, Na
dc.contributor.author赵娜
dc.contributor.authorZhao, Yang
dc.contributor.authorYu, Chundong
dc.date.accessioned2012-08-03T12:08:41Z
dc.date.available2012-08-03T12:08:41Z
dc.date.issued2011-05-17
dc.identifier.citationBiochemical and Biophysical Research Communications.June 2011,Volume 409, Issue 4, Pages 651–656zh_CN
dc.identifier.issn0006-291X
dc.identifier.urihttp://dx.doi.org/doi:10.1016/j.bbrc.2011.05.059
dc.identifier.uriWOS:000292358500011
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/13412
dc.description.abstractFibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD. (C) 2011 Elsevier Inc. All rights reserved.zh_CN
dc.description.sponsorshipACADEMIC PRESS INC ELSEVIER SCIENCEzh_CN
dc.language.isoenzh_CN
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCEzh_CN
dc.subjectFGFR4zh_CN
dc.subjectExtracellular domainzh_CN
dc.subjectNAFLDzh_CN
dc.subjectPPAR alphazh_CN
dc.titleSoluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver diseasezh_CN
dc.typeArticlezh_CN


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