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https://doi.org/10.1038/srep08134
Title: | The short-chain fatty acid receptor GPR43 is transcriptionally regulated by XBP1 in human monocytes | Authors: | Ang, Zhiwei Er, Jun Zhi Ding, Jeak Ling |
Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics UNFOLDED PROTEIN RESPONSE INTESTINAL INFLAMMATION GENE-EXPRESSION GUT MICROBIOTA ER STRESS ACTIVATION CELLS IMMUNITY NFAT PHOSPHORYLATION |
Issue Date: | 30-Jan-2015 | Publisher: | NATURE PUBLISHING GROUP | Citation: | Ang, Zhiwei, Er, Jun Zhi, Ding, Jeak Ling (2015-01-30). The short-chain fatty acid receptor GPR43 is transcriptionally regulated by XBP1 in human monocytes. SCIENTIFIC REPORTS 5 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/srep08134 | Abstract: | G-protein coupled receptor 43 (GPR43) recognizes short chain fatty acids and is implicated in obesity, colitis, asthma and arthritis. Here, we present the first full characterization of the GPR43 promoter and 5′-UTR. 5′-RACE of the GPR43 transcript identified the transcription start site (TSS) and a 124 bp 5′-UTR followed by a 1335 bp intron upstream of the ATG start codon. The sequence spanning-4560 to +68 bp relative to the GPR43 TSS was found to contain strong promoter activity, increasing luciferase reporter expression by >100-fold in U937 monocytes. Stepwise deletions further narrowed the putative GPR43 promoter (-451 to +68). Site-directed mutagenesis identified XBP1 as a core cis element, the mutation of which abrogated transcriptional activity. Mutations of predicted CREB, CHOP, NFAT and STAT5 binding sites, partially reduced promoter activity. ChIP assays confirmed the binding of XBP1 to the endogenous GPR43 promoter. Consistently, GPR43 expression is reduced in monocytes upon siRNA-knockdown of XBP1, while A549 cells overexpressing XBP1 displayed elevated GPR43 levels. Based on its ability to activate XBP1, we predicted and confirmed that TNFα induces GPR43 expression in human monocytes. Altogether, our findings form the basis for strategic modulation of GPR43 expression, with a view to regulate GPR43-associated diseases. | Source Title: | SCIENTIFIC REPORTS | URI: | https://scholarbank.nus.edu.sg/handle/10635/193857 | ISSN: | 20452322 | DOI: | 10.1038/srep08134 |
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SREP-GPR43-Sci. Rep. 5, 8134. doi 10.1038 srep08134.pdf | 2.67 MB | Adobe PDF | OPEN | Published | View/Download |
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