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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-...

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Autores principales: Lin, Xiuhong, Cheng, Lin, Wan, Yan, Yan, Yuerong, Zhang, Zhuo, Li, Xiaohui, Wu, Jiayun, Wang, Xiaoyi, Xu, Mingtong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2023
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.
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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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