Browsing by Author "Yu, Jie"

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    Growth Hormone Stimulates Transcription of the Fibroblast Growth Factor 21 Gene in the Liver through the Signal Transducer and Activator of Transcription 5
    Yu, Jie; Zhao, Lidan; Wang, Aihua; Eleswarapu, Satyanarayana; Ge, Xiaomei; Chen, Daiwen; Jiang, Honglin (Endocrine Society, 2012-02)
    Fibroblast 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)
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    Growth Hormone-Activated STAT5 May Indirectly Stimulate IGF-I Gene Transcription through HNF-3 gamma
    Eleswarapu, Satyanarayana; Ge, Xiaomei; Wang, Ying; Yu, Jie; Jiang, Honglin (Endocrine Society, 2009-12)
    IGF-I is abundantly expressed in the liver under the stimulation of GH. We showed previously that expression of hepatocyte nuclear factor (HNF)-3 gamma, a liver-enriched transcription factor, was strongly stimulated by GH in bovine liver. In this study, we determined whether GH-increased HNF-3 gamma might contribute to GH stimulation of IGF-I gene expression in bovine liver and the underlying mechanism. A sequence analysis of the bovine IGF-I promoter revealed three putative HNF-3 binding sites, which all appear to be conserved in mammals. Chromatin immunoprecipitation assays showed that GH injection increased binding of HNF-3 gamma to the IGF-I promoter in bovine liver. Gel-shift assays indicated that one of the three putative HNF-3 binding sites, HNF-3 binding site 1, bound to the HNF-3 gamma protein from bovine liver with high affinity. Cotransfection analyses demonstrated that this HNF-3 binding site was essential for the transcriptional response of the IGF-I promoter to HNF-3 gamma in CHO cells and to GH in primary mouse hepatocytes. Using similar approaches, we found that GH increased binding of the signal transducer and activator of transcription 5 (STAT5) to the HNF-3 gamma promoter in bovine liver, that this binding occurred at a conserved STAT5 binding site, and that this STAT5 binding site was necessary for the HNF-3 gamma promoter to respond to GH. Taken together, these results suggest that in addition to direct action, GH-activated STAT5 may also indirectly stimulate IGF-I gene transcription in the liver by directly enhancing the expression of the HNF-3 gamma gene. (Molecular Endocrinology 23: 2026-2037, 2009)
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    Phytoestrogen Genistein Up-Regulates Endothelial Nitric Oxide Synthase Expression Via Activation of cAMP Response Element-Binding Protein in Human Aortic Endothelial Cells
    Si, Hongwei; Yu, Jie; Jiang, Honglin; Lum, Hazel; Liu, Dongmin (Endocrine Society, 2012-07)
    We previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in primary human aortic endothelial cells. Inhibition of extracellular signal regulated kinase, phosphoinositol-3 kinase, or protein kinase C did not affect genistein-enhanced eNOS expression and NO synthesis. However, chemical inhibition of protein kinase A (PKA) or adenoviral transfer of the specific endogenous PKA inhibitor gene completely abolished PKA activity and genistein-stimulated eNOS expression and NO production. Accordingly, genistein induced PKA activity and subsequent phosphorylation of cAMP response element (CRE)-binding protein (CREB) at Ser133. Suppression of CREB by small interfering RNA transfection abolished genistein-enhanced eNOS expression and NO production. Consistently, deletion of the CRE site within human eNOS promoter eliminated genistein-stimulated eNOS promoter activity. These findings provide the first evidence to our knowledge that genistein may play a beneficial role in vascular function through targeting the PKA/CREB/eNOS/NO signaling pathway. (Endocrinology 153: 3190-3198, 2012)
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    Regulation of fibroblast growth factor 15/19 and 21 on metabolism: in the fed or fasted state
    Guan, Dandan; Zhao, Lidan; Chen, Daiwen; Yu, Bing; Yu, Jie (2016-03-01)
    Fibroblast growth factor (FGF) 15/19 and FGF21 are two atypical members of FGF19 subfamily that function as hormones. Exogenous FGF15/19 and FGF21 have pharmacological effects, and endogenous FGF15/19 and FGF21 play vital roles in the maintenance of energy homeostasis. Recent reports have expanded the effects of FGF15/19 and FGF21 on carbohydrate and lipid metabolism. However, the regulations of FGF15/19 and FGF21 on metabolism are different. FGF15/19 is mainly secreted from the small intestine in response to feeding, and FGF21 is secreted from the liver in response to extended fasting and from the liver and adipose tissue in response to feeding. In this work, we reviewed the regulatory effects of FGF15/19 and FGF21 on metabolism in the fast and fed states. This information may provide some insight into the metabolic regulation of FGF15/19 and FGF21 in different physiological condition.