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Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells
BACKGROUND: The RAS system is involved in the regulation of islet function, but its regulation remains unclear. OBJECTIVE: This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet β-cells. METHODS: miR-375 mimics and inhibitors were transfected into insulin-...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514520/ https://www.ncbi.nlm.nih.gov/pubmed/36748222 http://dx.doi.org/10.2174/1871530323666230206121715 |
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author | Lin, Xiuhong Cheng, Lin Wan, Yan Yan, Yuerong Zhang, Zhuo Li, Xiaohui Wu, Jiayun Wang, Xiaoyi Xu, Mingtong |
author_facet | Lin, Xiuhong Cheng, Lin Wan, Yan Yan, Yuerong Zhang, Zhuo Li, Xiaohui Wu, Jiayun Wang, Xiaoyi Xu, Mingtong |
author_sort | Lin, Xiuhong |
collection | PubMed |
description | BACKGROUND: The RAS system is involved in the regulation of islet function, but its regulation remains unclear. OBJECTIVE: This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet β-cells. METHODS: miR-375 mimics and inhibitors were transfected into insulin-secreting MIN6 cells in the presence or absence of RAS component. RESULTS: Compared to control, in Ang II-treated MIN6 cells, miR-375 mimic transfection results in a decrement in cell viability and Akt-Ser levels (0.739±0.05 vs. 0.883±0.06 and 0.40±0.04 vs. 0.79±0.04, respectively), while the opposite occurred in miR-375 inhibitor-transfected cells (1.032±0.11 vs. 0.883±0.06 and 0.98±0.05 vs. 0.79±0.04, respectively, P<0.05). Mechanistically, transfection of miR-375 mimics into Ang II-treated MIN6 cells significantly reduced the expression of Mapkap1 protein (0.97±0.15 vs. 0.63±0.06, P<0.05); while miR-375 inhibitor-transfected cells elevated Mapkap1 expression level (0.35±0.11 vs. 0.90±0.05, P<0.05), without changes in mRNA expression. Transfection of miR-375 specific inhibitors TSB-Mapkap1 could elevate Mapkap1 (1.62±0.02 vs. 0.68±0.01, P<0.05), while inhibition of Mapkap1 could significantly reduce the level of Akt-Ser473 phosphorylation (0.60±0.14 vs. 1.80±0.27, P<0.05). CONCLUSION: The effects of Ang II on mouse islet β cells were mediated by miR-375 through miR-375/Mapkap 1 axis. This targeted regulation may occur by affecting Akt phosphorylation of β cells. These results may provide new ideas and a scientific basis for further development of miRNA-targeted islet protection measures. |
format | Online Article Text |
id | pubmed-10514520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-105145202023-09-23 Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells Lin, Xiuhong Cheng, Lin Wan, Yan Yan, Yuerong Zhang, Zhuo Li, Xiaohui Wu, Jiayun Wang, Xiaoyi Xu, Mingtong Endocr Metab Immune Disord Drug Targets Pharmacology, Medicine, Endocrinology, Immunology, Inflammation & Allergy, Biochemistry and Molecular Biology BACKGROUND: The RAS system is involved in the regulation of islet function, but its regulation remains unclear. OBJECTIVE: This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet β-cells. METHODS: miR-375 mimics and inhibitors were transfected into insulin-secreting MIN6 cells in the presence or absence of RAS component. RESULTS: Compared to control, in Ang II-treated MIN6 cells, miR-375 mimic transfection results in a decrement in cell viability and Akt-Ser levels (0.739±0.05 vs. 0.883±0.06 and 0.40±0.04 vs. 0.79±0.04, respectively), while the opposite occurred in miR-375 inhibitor-transfected cells (1.032±0.11 vs. 0.883±0.06 and 0.98±0.05 vs. 0.79±0.04, respectively, P<0.05). Mechanistically, transfection of miR-375 mimics into Ang II-treated MIN6 cells significantly reduced the expression of Mapkap1 protein (0.97±0.15 vs. 0.63±0.06, P<0.05); while miR-375 inhibitor-transfected cells elevated Mapkap1 expression level (0.35±0.11 vs. 0.90±0.05, P<0.05), without changes in mRNA expression. Transfection of miR-375 specific inhibitors TSB-Mapkap1 could elevate Mapkap1 (1.62±0.02 vs. 0.68±0.01, P<0.05), while inhibition of Mapkap1 could significantly reduce the level of Akt-Ser473 phosphorylation (0.60±0.14 vs. 1.80±0.27, P<0.05). CONCLUSION: The effects of Ang II on mouse islet β cells were mediated by miR-375 through miR-375/Mapkap 1 axis. This targeted regulation may occur by affecting Akt phosphorylation of β cells. These results may provide new ideas and a scientific basis for further development of miRNA-targeted islet protection measures. Bentham Science Publishers 2023-07-19 2023-07-19 /pmc/articles/PMC10514520/ /pubmed/36748222 http://dx.doi.org/10.2174/1871530323666230206121715 Text en © 2023 Bentham Science Publishers https://creativecommons.org/licenses/by/4.0/© 2023 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode) |
spellingShingle | Pharmacology, Medicine, Endocrinology, Immunology, Inflammation & Allergy, Biochemistry and Molecular Biology Lin, Xiuhong Cheng, Lin Wan, Yan Yan, Yuerong Zhang, Zhuo Li, Xiaohui Wu, Jiayun Wang, Xiaoyi Xu, Mingtong Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells |
title | Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells |
title_full | Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells |
title_fullStr | Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells |
title_full_unstemmed | Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells |
title_short | Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells |
title_sort | ang ii controls the expression of mapkap1 by mir-375 and affects the function of islet β cells |
topic | Pharmacology, Medicine, Endocrinology, Immunology, Inflammation & Allergy, Biochemistry and Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514520/ https://www.ncbi.nlm.nih.gov/pubmed/36748222 http://dx.doi.org/10.2174/1871530323666230206121715 |
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