Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells
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 gen...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/173058 |
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| author | Akiyo Yamauchi Asako Itaya-Hironaka Sumiyo Sakuramoto-Tsuchida Maiko Takeda Kiyomi Yoshimoto Tomoko Miyaoka Takanori Fujimura Hiroki Tsujinaka Chikatsugu Tsuchida Hiroyo Ota Shin Takasawa |
| author_facet | Akiyo Yamauchi Asako Itaya-Hironaka Sumiyo Sakuramoto-Tsuchida Maiko Takeda Kiyomi Yoshimoto Tomoko Miyaoka Takanori Fujimura Hiroki Tsujinaka Chikatsugu Tsuchida Hiroyo Ota Shin Takasawa |
| author_sort | Akiyo Yamauchi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4c6275ea93a94a5fb888a8b4560d1ee6 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-4c6275ea93a94a5fb888a8b4560d1ee62025-02-03T00:59:47ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/173058173058Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β CellsAkiyo Yamauchi0Asako Itaya-Hironaka1Sumiyo Sakuramoto-Tsuchida2Maiko Takeda3Kiyomi Yoshimoto4Tomoko Miyaoka5Takanori Fujimura6Hiroki Tsujinaka7Chikatsugu Tsuchida8Hiroyo Ota9Shin Takasawa10Department of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanDepartment of Biochemistry, Nara Medical University, Kashihara 634-8521, JapanReg (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.http://dx.doi.org/10.1155/2015/173058 |
| spellingShingle | Akiyo Yamauchi Asako Itaya-Hironaka Sumiyo Sakuramoto-Tsuchida Maiko Takeda Kiyomi Yoshimoto Tomoko Miyaoka Takanori Fujimura Hiroki Tsujinaka Chikatsugu Tsuchida Hiroyo Ota Shin Takasawa Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells Journal of Diabetes Research |
| title | Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells |
| title_full | Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells |
| title_fullStr | Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells |
| title_full_unstemmed | Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells |
| title_short | Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells |
| title_sort | synergistic activations of reg iα and reg iβ promoters by il 6 and glucocorticoids through jak stat pathway in human pancreatic β cells |
| url | http://dx.doi.org/10.1155/2015/173058 |
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