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Several transcription factors regulate COX-2 gene expression in pancreatic β-cells

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Abstract

Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreatic β-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impair β-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. In this report, we used pancreatic β-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 β-cells. Moreover, these transcriptional regulators of COX-2 expression will be potential targets for the prevention of β-cell damage mediated by PGE2.

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Abbreviations

COX-2:

Cyclooxygenase-2

PGE2:

Prostaglandin E2

CREB:

Cyclic AMP response-element binding protein

STAT1:

Signal transducer and activator of transcription 1

MAPK:

Mitogen-activated protein kinase

ERKs:

Extracellular signal-regulated kinases

JNK:

c-Jun N-terminal kinase

JAK:

Janus kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

CaMK:

Calmodulin kinase

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (30370676).

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Authors and Affiliations

  1. Key Laboratory of Human Functional Genomics of Jiangsu Province, Hanzhong Rd. #140, Nanjing, 210029, P.R. China

    Xiongfei Zhang, Xiaomin Yang & Xiao Han

  2. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Rd. #300, Nanjing, 210029, P.R. China

    Jingjing Zhang

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  1. Xiongfei Zhang
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  2. Jingjing Zhang
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  3. Xiaomin Yang
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Correspondence to Xiao Han.

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Xiongfei Zhang and Jingjing Zhang are equal contributors.

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Zhang, X., Zhang, J., Yang, X. et al. Several transcription factors regulate COX-2 gene expression in pancreatic β-cells. Mol Biol Rep 34, 199–206 (2007). https://doi.org/10.1007/s11033-007-9085-3

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