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MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells
Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204315/ https://www.ncbi.nlm.nih.gov/pubmed/27737950 http://dx.doi.org/10.2337/db16-0592 |
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author | Grieco, Fabio Arturo Sebastiani, Guido Juan-Mateu, Jonas Villate, Olatz Marroqui, Laura Ladrière, Laurence Tugay, Ksenya Regazzi, Romano Bugliani, Marco Marchetti, Piero Dotta, Francesco Eizirik, Décio L. |
author_facet | Grieco, Fabio Arturo Sebastiani, Guido Juan-Mateu, Jonas Villate, Olatz Marroqui, Laura Ladrière, Laurence Tugay, Ksenya Regazzi, Romano Bugliani, Marco Marchetti, Piero Dotta, Francesco Eizirik, Décio L. |
author_sort | Grieco, Fabio Arturo |
collection | PubMed |
description | Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target genes remain to be clarified. We performed an miRNA expression profile on human islet preparations exposed to the cytokines IL-1β plus IFN-γ. Confirmation of miRNA and target gene modification in human β-cells was performed by real-time quantitative PCR. Single-stranded miRNAs inhibitors were used to block selected endogenous miRNAs. Cell death was measured by Hoechst/propidium iodide staining and activation of caspase-3. Fifty-seven miRNAs were detected as modulated by cytokines. Three of them, namely miR-23a-3p, miR-23b-3p, and miR-149-5p, were downregulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human β-cell apoptosis. These results identify a novel cross talk between a key family of miRNAs and proapoptotic Bcl-2 proteins in human pancreatic β-cells, broadening our understanding of cytokine-induced β-cell apoptosis in early T1D. |
format | Online Article Text |
id | pubmed-5204315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-52043152018-01-01 MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells Grieco, Fabio Arturo Sebastiani, Guido Juan-Mateu, Jonas Villate, Olatz Marroqui, Laura Ladrière, Laurence Tugay, Ksenya Regazzi, Romano Bugliani, Marco Marchetti, Piero Dotta, Francesco Eizirik, Décio L. Diabetes Islet Studies Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target genes remain to be clarified. We performed an miRNA expression profile on human islet preparations exposed to the cytokines IL-1β plus IFN-γ. Confirmation of miRNA and target gene modification in human β-cells was performed by real-time quantitative PCR. Single-stranded miRNAs inhibitors were used to block selected endogenous miRNAs. Cell death was measured by Hoechst/propidium iodide staining and activation of caspase-3. Fifty-seven miRNAs were detected as modulated by cytokines. Three of them, namely miR-23a-3p, miR-23b-3p, and miR-149-5p, were downregulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human β-cell apoptosis. These results identify a novel cross talk between a key family of miRNAs and proapoptotic Bcl-2 proteins in human pancreatic β-cells, broadening our understanding of cytokine-induced β-cell apoptosis in early T1D. American Diabetes Association 2017-01 2016-10-13 /pmc/articles/PMC5204315/ /pubmed/27737950 http://dx.doi.org/10.2337/db16-0592 Text en © 2017 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. |
spellingShingle | Islet Studies Grieco, Fabio Arturo Sebastiani, Guido Juan-Mateu, Jonas Villate, Olatz Marroqui, Laura Ladrière, Laurence Tugay, Ksenya Regazzi, Romano Bugliani, Marco Marchetti, Piero Dotta, Francesco Eizirik, Décio L. MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells |
title | MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells |
title_full | MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells |
title_fullStr | MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells |
title_full_unstemmed | MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells |
title_short | MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells |
title_sort | micrornas mir-23a-3p, mir-23b-3p, and mir-149-5p regulate the expression of proapoptotic bh3-only proteins dp5 and puma in human pancreatic β-cells |
topic | Islet Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204315/ https://www.ncbi.nlm.nih.gov/pubmed/27737950 http://dx.doi.org/10.2337/db16-0592 |
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