An essential role of cAMP response element-binding protein in epidermal growth factor-mediated induction of sodium/glucose cotransporter 1 gene expression and intestinal glucose uptake |
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Affiliation: | 1. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC;2. School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC;3. Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, ROC;4. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC;5. School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC;6. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC;1. Behavioral and Cognitive Neuroscience Cluster, Psychology Doctoral Program, The Graduate Center and Department of Psychology, New York, NY, USA;2. Queens College, City University of New York, New York, NY, USA;1. Department of Plastic Surgery, The Second Hospital of Harbin Medical University, PR China;2. Department of Breast Surgery, The Second Hospital of Harbin Medical University, PR China;3. Section of Hematology/Oncology, Stephenson Cancer Center, Department of Internal Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, USA;1. Genomic Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA;2. Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77024, USA |
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Abstract: |  The sodium/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. Its expression is decreased in individuals with intestinal inflammatory disorders and is correlated with the pathogenesis of disease. The aim of this study was to understand the regulatory mechanism of the SGLT1 gene. Using the trinitrobenzene sulfonic acid-induced mouse models of intestinal inflammation, we observed decreased SGLT1 expression in the inflamed intestine was positively correlated with the mucosal level of epidermal growth factor (EGF) and activated CREB. Overexpression of EGF demonstrated that the effect of EGF on intestinal glucose uptake was primarily due to the increased level of SGLT1. We identified an essential cAMP binding element (CRE) confers EGF inducibility in the human SGLT1 gene promoter. ChIP assay further demonstrated the increased binding of CREB and CBP to the SGLT1 gene promoter in EGF-treated cells. In addition, the EGFR- and PI3K-dependent CREB phosphorylations are involved in the EGF-mediated SGLT1 expression. This is the first report to demonstrate that CREB is involved in EGF-mediated transcription regulation of SGLT1 gene in the normal and inflamed intestine, which can provide potential therapeutic applications for intestinal inflammatory disorders. |
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Keywords: | Caco-2 cells Gene expression Glucose transporter Sodium/glucose cotransporter 1 promoter Transcriptional factors |
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