Several transcription factors regulate COX-2 gene expression in pancreatic beta-cells.
Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreatic beta-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impair beta-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. In this report, we used pancreatic beta-cells (RINm5F) to explore the potential transcription factors regulating COX-2 promoter activity. Using promoter screening method, we selected several transcription factors in our study. Through luciferase reporter studies, we found that these factors can regulate COX-2 promoter activity in RINm5F cells. Among these factors, cyclic AMP response-element binding protein (CREB), Ets family members Ets-1 and Elk-1 can positively regulate COX-2 promoter activity. On the contrary, signal transducer and activator of transcription 1 (STAT1) plays a negative role on COX-2 promoter. Our findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreatic beta-cells. Moreover, these transcriptional regulators of COX-2 expression will be potential targets for the prevention of beta-cell damage mediated by PGE2.
Zhang
Xiongfei
X
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing, PR China.
Zhang
Jingjing
J
Yang
Xiaomin
X
Han
Xiao
X
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D050417:Insulin-Secreting Cells / Q000201:enzymology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1 / Q000502:physiology; D051381:Rats; D050794:STAT1 Transcription Factor / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D050807:ets-Domain Protein Elk-1 / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; C494043:Ets1 protein, rat; D050784:Proto-Oncogene Protein c-ets-1; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D051546:Cyclooxygenase 2