Growth Hormone Stimulates Transcription of the Fibroblast Growth Factor 21 Gene in the Liver through the Signal Transducer and Activator of Transcription 5

dc.contributor.authorYu, Jieen
dc.contributor.authorZhao, Lidanen
dc.contributor.authorWang, Aihuaen
dc.contributor.authorEleswarapu, Satyanarayanaen
dc.contributor.authorGe, Xiaomeien
dc.contributor.authorChen, Daiwenen
dc.contributor.authorJiang, Honglinen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:18Zen
dc.date.available2014-07-08T13:02:18Zen
dc.date.issued2012-02en
dc.description.abstractFibroblast growth factor 21 (FGF21) is a recently discovered metabolic regulator. Interestingly, FGF21 is also known to inhibit Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling from the GH receptor in the liver, where FGF21 mRNA is predominantly expressed. In this study, we tested the hypothesis that FGF21 gene expression in the liver is controlled by GH through STAT5. We found that GH injection to cattle increased FGF21 mRNA expression in the liver. Mapped by a 5'-rapid amplification of cDNA ends assay, transcription of the FGF21 gene in the bovine liver was mainly initiated from a nucleotide 24 bp downstream of a TATA box. The bovine FGF21 promoter contains three putative STAT5-binding sites. EMSA confirmed the ability of them to bind to liver STAT5 protein from GH-injected cattle. Chromatin immunoprecipitation assays demonstrated that GH administration increased the binding of STAT5 to the FGF21 promoter in the liver. Cotransfection analyses showed that GH induced reporter gene expression from the FGF21 promoter in a STAT5-dependent manner. GH also stimulated FGF21 mRNA expression in cultured mouse hepatocytes. These data together indicate that GH directly stimulates FGF21 gene transcription in the liver, at least in part, through STAT5. This finding, together with the fact that FGF21 inhibits GH-induced JAK2-STAT5 signaling in the liver, suggests a novel negative feedback loop that prevents excessive JAK2-STAT5 signaling from the GH receptor in the liver. (Endocrinology 153: 750-758, 2012)en
dc.description.sponsorshipUS Department of Agriculture National Institute of Food and Agriculture 2009-35205-05221en
dc.description.sponsorshipChina Scholarship Councilen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationJie Yu, Lidan Zhao, Aihua Wang, Satyanarayana Eleswarapu, Xiaomei Ge, Daiwen Chen, and Honglin Jiang, "Growth Hormone Stimulates Transcription of the Fibroblast Growth Factor 21 Gene in the Liver through the Signal Transducer and Activator of Transcription 5," Endocrinology 2012 153:2, 750-758. DOI: http://dx.doi.org/10.1210/en.2011-1591.en
dc.identifier.doihttps://doi.org/10.1210/en.2011-1591en
dc.identifier.issn0013-7227en
dc.identifier.urihttp://hdl.handle.net/10919/49396en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/en.2011-1591en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectfactor-ien
dc.subjectbinding-sitesen
dc.subjectigf-ien
dc.subjectexpressionen
dc.subjectreceptoren
dc.subjectghen
dc.subjectstat5ben
dc.subjectidentificationen
dc.subjectvivoen
dc.subjectmetabolismen
dc.subjectendocrinology & metabolismen
dc.titleGrowth Hormone Stimulates Transcription of the Fibroblast Growth Factor 21 Gene in the Liver through the Signal Transducer and Activator of Transcription 5en
dc.title.serialEndocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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