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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
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نویسنده
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yamauchi a. ,itaya-hironaka a. ,sakuramoto-tsuchida s. ,takeda m. ,yoshimoto k. ,miyaoka t. ,fujimura t. ,tsujinaka h. ,tsuchida c. ,ota h. ,takasawa s.
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منبع
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journal of diabetes research - 2015 - دوره : 2015 - شماره : 0
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چکیده
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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 and reg iβ should be upregulated in human β cells under inflammatory conditions through the jak/stat pathway. © 2015 akiyo yamauchi et al.
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آدرس
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department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan, department of biochemistry,nara medical university, Japan
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Authors
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