Synergistic activations of REG I α and REG I β promoters by IL-6 and Glucocorticoids through JAK/STAT pathway in human pancreatic β cells

Journal of Diabetes Research
Akiyo YamauchiS Takasawa

Abstract

Reg (Regenerating gene) gene was originally isolated from rat regenerating islets and its encoding protein was revealed as an autocrine/paracrine growth factor for β cells. Rat Reg gene is activated in inflammatory conditions for β cell regeneration. In human, although five functional REG family genes (REG Iα, REG Iβ, REG III, HIP/PAP, and REG IV) were isolated, their expressions in β cells under inflammatory conditions remained unclear. In this study, we found that combined addition of IL-6 and dexamethasone (Dx) induced REG Iα and REG Iβ expression in human 1.1B4 β cells. Promoter assay revealed that a signal transducer and activator of transcription- (STAT-) binding site in each promoter of REG Iα (TGCCGGGAA) and REG Iβ (TGCCAGGAA) was essential for the IL-6+Dx-induced promoter activation. A Janus kinase 2 (JAK2) inhibitor significantly inhibited the IL-6+Dx-induced REG Iα and REG Iβ transcription. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that IL-6+Dx stimulation increased STAT3 binding to the REG Iα promoter. Furthermore, small interfering RNA-mediated targeting of STAT3 blocked the IL-6+Dx-induced expression of REG Iα and REG Iβ. These results indicate that the expression of REG Iα an...Continue Reading

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Citations

Nov 22, 2015·Expert Opinion on Therapeutic Targets·Shin Takasawa
Feb 18, 2017·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·J GengX-D Yao
Oct 28, 2017·International Journal of Molecular Sciences·Yasuaki TohmaHajime Ohgushi
Dec 12, 2017·Acta Physiologica·A D GreenP R Flatt
Nov 7, 2019·International Journal of Molecular Sciences·Juria AkasakaHiroshi Kobayashi
Nov 17, 2015·Diabetology & Metabolic Syndrome·Sadaf Saleem UppalBushra Chaudhry
Sep 17, 2016·International Journal of Oncology·Shinji MikamiTadashi Kitahara
Apr 25, 2019·International Journal of Molecular Sciences·Tomoko UchiyamaShin Takasawa
Nov 2, 2017·Biochemistry and Biophysics Reports·Chikatsugu TsuchidaShin Takasawa

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Methods Mentioned

BETA
PCR
Assay
Immunoprecipitation
electrophoresis
ChIP
immunoprecipitations

Software Mentioned

GraphPad Prism

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