C/EBPβ regulates P2X7 receptor expression in response to glucose challenge in intestinal epithelial cells.
Activation of the ATP-dependent P2X7 receptor modulates glucose transport in intestinal epithelial cells through the downregulation of glucose transporter GLUT2. In the present study, we show that an increase in glucose concentration stimulates P2X7 receptor transcription via modulation of CCAAT/enhancer binding proteins (C/EBPs) α and β expression. The described human P2X7 receptor promoter region (GenBank Y12851) was cloned upstream of a luciferase reporter gene in pGL4.10 plasmid and used to determine whether C/EBPs, namely C/EBPα and C/EBPβ, are able to stimulate the transcription of P2X7 receptor. Results show that C/EBPβ was the main regulator of P2X7 receptor expression in response to a glucose challenge. Chromatin immunoprecipitation (ChIP) assays further revealed that C/EBPβ occupied the -213 to +6 nt P2X7 promoter region. Surprisingly, C/EBPα was also able to bind this region as revealed by ChIP assays, but without inducing receptor transcription. In fact, C/EBPα and the C/EBPβ-LIP isoform blocked the C/EBPβ-dependent regulation of P2X7 receptor transcription. These findings suggest that glucose is not only the major source of energy for cell function but may also act as a signaling molecule to stimulate the expression of regulatory proteins.
Department of Anatomy and Cell Biology, Faculté de Médecine et des Sciences de la Santé, Pavillon de Recherche Appliquée sur le Cancer, Université de Sherbrooke, Sherbrooke, 3201 Jean-Mignault, QC J1E 4K8, Canada.
Maude S
MS
Bilodeau
Guillaume
G
Arguin
Fernand-Pierre
FP
Gendron
D000818:Animals; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C545013:Cebpb protein, mouse; C545014:Cebpb protein, rat; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D058486:Receptors, Purinergic P2X7; D005947:Glucose
C/EBP; P2X receptor; cellules épithéliales intestinales; gene regulation; glucose; intestinal epithelial cells; récepteur P2X; régulation génique