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Abstract Increased cyclooxygenase-2 (COX-2) expression is associated with pancreatic β-cell dysfunction. We previously demonstrated that the transcription factor Ets-1 significantly up-regulated COX-2 gene promoter activity. In this report, we used the pa



Published on:2016-11-28   Views:323

Abstract

Increased cyclooxygenase-2 (COX-2)expression is associated with pancreatic β-cell dysfunction. We previouslydemonstrated that the transcription factor Ets-1 significantly up-regulatedCOX-2 gene promoter activity. In this report, we used the pancreatic β-cellline INS-1 and isolated rat islets to investigate whether Ets-1 could induceβ-cell dysfunction through up-regulating COX-2 gene expression. We investigatedthe effects of ETS-1 overexpression and the effects of ETS-1 RNA interferenceon endogenous COX-2 expression in INS-1 cells. We used site-directedmutagenesis and a dual luciferase reporter assay to study putative Ets-1binding sites in the COX-2 promoter. The effect of ETS-1 1 overexpression onthe insulin secretion function of INS-1 cells and rat islets and the potentialreversal of these effects by a COX-2 inhibitor were determined in aglucose-stimulated insulin secretion (GSIS) assay. ETS-1 overexpressionsignificantly induces endogenous COX-2 expression, but ETS-1 RNA interferencehas no effect on basal COX-2 expression in INS-1 cells. Ets-1 proteinsignificantly increases COX-2 promoter activity through the binding sitelocated in the -195/-186 region of the COX-2 promoter. ETS-1 overexpressionsignificantly inhibited the GSIS function of INS-1 cells and islet cells andCOX-2 inhibitor treatment partly reversed this effect. These findings indicatedthat ETS-1 overexpression induces β-cell dysfunction partly throughup-regulation of COX-2 gene expression. Moreover, Ets-1, the transcriptionalregulator of COX-2 expression, may be a potential target for the prevention ofβ-cell dysfunction mediated by COX-2.