IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway
Xinhua Wu,1 Tao Yu,1 Ning Ji,1 Yujie Huang,1 Lingcheng Gao,1 Wen Shi,1 Yan Yan,1 Hang Li,1 Liming Ma,1 Kede Wu,2 Zhen Wu31Department of Endocrinology, Huaian Hospital of Huaian District, Huaian, Jiangsu 223200, People’s Republic of China; 2Clinical Medicine, Medical College of Yangzhou Uni...
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Dove Medical Press
2019
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oai:doaj.org-article:f46ee125d63b4f8abfcb60ddb1e8a97e2021-12-02T00:14:19ZIL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway1178-7007https://doaj.org/article/f46ee125d63b4f8abfcb60ddb1e8a97e2019-08-01T00:00:00Zhttps://www.dovepress.com/il6r-inhibits-viability-and-apoptosis-of-pancreatic-beta-cells-in-type-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Xinhua Wu,1 Tao Yu,1 Ning Ji,1 Yujie Huang,1 Lingcheng Gao,1 Wen Shi,1 Yan Yan,1 Hang Li,1 Liming Ma,1 Kede Wu,2 Zhen Wu31Department of Endocrinology, Huaian Hospital of Huaian District, Huaian, Jiangsu 223200, People’s Republic of China; 2Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu 225009, People’s Republic of China; 3Electric Engineering, China University of Mining and Technology, Xuzhou, Jiangsu 221116, People’s Republic of ChinaCorrespondence: Xinhua WuDepartment of Endocrinology, Huaian Hospital of Huaian District, 50 Meters North of Huaihe Road, Huaian 223200, People’s Republic of ChinaTel +865 178 593 9208Email wuxh8686@163.comBackground and aim: Type 2 diabetes mellitus (T2DM) is a common disease of harming to people’s health. MicroRNAs have recently been considered as key regulators of many biological processes, such as cell proliferation, migration and apoptosis. However, the effect of miR-22 expression by targeting IL6 receptor (IL6R) in T2DM and potential molecular mechanism involved remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 by targeting IL6R in pancreatic beta-cells viability and apoptosis of T2DM.Methods: The expressions of miR-22, IL6R and apolipoprotein (apoA1, apoB and apoE) were examined by reverse transcription-quantitative PCR (qRT-PCR). Pancreatic beta-cells were transiently transfected with a miR-22 mimic or si-IL6R plasmid which validated with qRT-PCR to analyze the expression of miR-22 or IL6R. Cell viability, apoptosis and protein expression levels were determined by CCK-8, flow cytometry and Western blotting, respectively.Results: The proportion of INS-1E cell apoptosis was increased in islets of diabetic rats. Furthermore, miR-22 was downregulated and IL6R was upregulated in both diabetic serum and glucose-induced INS-1E cells. miR-22 overexpression or IL6R inhibition significantly strengthened cell viability and reduced the expression of apoptosis-related proteins to suppress cell apoptosis. IL6R was demonstrated as a target gene of miR-22 which could negatively regulate IL6R expression. Moreover, phosphorylation of JAK/STAT signaling pathway was activated by miR-22 overexpression or IL6R inhibition to strengthen the viability and suppress apoptosis of INS-1E cells.Conclusion: This study indicated that miR-22 strengthened the viability and suppressed apoptosis of INS-1E cells, partly by down-regulation of IL6R through the activation of JAK/STAT signaling pathway.Keywords: IL6R, pancreatic beta-cells, type 2 diabetes mellitus, JAK/STAT signaling pathway, miR-22Wu XYu TJi NHuang YGao LShi WYan YLi HMa LWu KWu ZDove Medical PressarticleIL6RPancreatic beta-cellsType 2 diabetes mellitusJAK/STAT signaling pathwaymiR-22Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 1645-1657 (2019) |
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IL6R Pancreatic beta-cells Type 2 diabetes mellitus JAK/STAT signaling pathway miR-22 Specialties of internal medicine RC581-951 |
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IL6R Pancreatic beta-cells Type 2 diabetes mellitus JAK/STAT signaling pathway miR-22 Specialties of internal medicine RC581-951 Wu X Yu T Ji N Huang Y Gao L Shi W Yan Y Li H Ma L Wu K Wu Z IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway |
| description |
Xinhua Wu,1 Tao Yu,1 Ning Ji,1 Yujie Huang,1 Lingcheng Gao,1 Wen Shi,1 Yan Yan,1 Hang Li,1 Liming Ma,1 Kede Wu,2 Zhen Wu31Department of Endocrinology, Huaian Hospital of Huaian District, Huaian, Jiangsu 223200, People’s Republic of China; 2Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu 225009, People’s Republic of China; 3Electric Engineering, China University of Mining and Technology, Xuzhou, Jiangsu 221116, People’s Republic of ChinaCorrespondence: Xinhua WuDepartment of Endocrinology, Huaian Hospital of Huaian District, 50 Meters North of Huaihe Road, Huaian 223200, People’s Republic of ChinaTel +865 178 593 9208Email wuxh8686@163.comBackground and aim: Type 2 diabetes mellitus (T2DM) is a common disease of harming to people’s health. MicroRNAs have recently been considered as key regulators of many biological processes, such as cell proliferation, migration and apoptosis. However, the effect of miR-22 expression by targeting IL6 receptor (IL6R) in T2DM and potential molecular mechanism involved remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 by targeting IL6R in pancreatic beta-cells viability and apoptosis of T2DM.Methods: The expressions of miR-22, IL6R and apolipoprotein (apoA1, apoB and apoE) were examined by reverse transcription-quantitative PCR (qRT-PCR). Pancreatic beta-cells were transiently transfected with a miR-22 mimic or si-IL6R plasmid which validated with qRT-PCR to analyze the expression of miR-22 or IL6R. Cell viability, apoptosis and protein expression levels were determined by CCK-8, flow cytometry and Western blotting, respectively.Results: The proportion of INS-1E cell apoptosis was increased in islets of diabetic rats. Furthermore, miR-22 was downregulated and IL6R was upregulated in both diabetic serum and glucose-induced INS-1E cells. miR-22 overexpression or IL6R inhibition significantly strengthened cell viability and reduced the expression of apoptosis-related proteins to suppress cell apoptosis. IL6R was demonstrated as a target gene of miR-22 which could negatively regulate IL6R expression. Moreover, phosphorylation of JAK/STAT signaling pathway was activated by miR-22 overexpression or IL6R inhibition to strengthen the viability and suppress apoptosis of INS-1E cells.Conclusion: This study indicated that miR-22 strengthened the viability and suppressed apoptosis of INS-1E cells, partly by down-regulation of IL6R through the activation of JAK/STAT signaling pathway.Keywords: IL6R, pancreatic beta-cells, type 2 diabetes mellitus, JAK/STAT signaling pathway, miR-22 |
| format |
article |
| author |
Wu X Yu T Ji N Huang Y Gao L Shi W Yan Y Li H Ma L Wu K Wu Z |
| author_facet |
Wu X Yu T Ji N Huang Y Gao L Shi W Yan Y Li H Ma L Wu K Wu Z |
| author_sort |
Wu X |
| title |
IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway |
| title_short |
IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway |
| title_full |
IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway |
| title_fullStr |
IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway |
| title_full_unstemmed |
IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway |
| title_sort |
il6r inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by mir-22 of the jak/stat signaling pathway |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/f46ee125d63b4f8abfcb60ddb1e8a97e |
| work_keys_str_mv |
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