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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2017
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.
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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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