Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells.

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Serval ID
serval:BIB_C0A5A6D4A84C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells.
Journal
Diabetes
Author(s)
Roggli E., Britan A., Gattesco S., Lin-Marq N., Abderrahmani A., Meda P., Regazzi R.
ISSN
1939-327X[electronic], 0012-1797[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
59
Number
4
Pages
978-986
Language
english
Abstract
OBJECTIVE: Pancreatic beta-cells exposed to proinflammatory cytokines display alterations in gene expression resulting in defective insulin secretion and apoptosis. MicroRNAs are small noncoding RNAs emerging as key regulators of gene expression. Here, we evaluated the contribution of microRNAs to cytokine-mediated beta-cell cytotoxicity. RESEARCH DESIGN AND METHODS: We used global microarray profiling and real-time PCR analysis to detect changes in microRNA expression in beta-cells exposed to cytokines and in islets of pre-diabetic NOD mice. We assessed the involvement of the microRNAs affected in cytokine-mediated beta-cell failure by modifying their expression in insulin-secreting MIN6 cells. RESULTS: We found that IL-1beta and TNF-alpha induce the expression of miR-21, miR-34a, and miR-146a both in MIN6 cells and human pancreatic islets. We further show an increase of these microRNAs in islets of NOD mice during development of pre-diabetic insulitis. Blocking miR-21, miR-34a, or miR-146a function using antisense molecules did not restore insulin-promoter activity but prevented the reduction in glucose-induced insulin secretion observed upon IL-1beta exposure. Moreover, anti-miR-34a and anti-miR-146a treatment protected MIN6 cells from cytokine-triggered cell death. CONCLUSIONS: Our data identify miR-21, miR-34a, and miR-146a as novel players in beta-cell failure elicited in vitro and in vivo by proinflammatory cytokines, notably during the development of peri-insulitis that precedes overt diabetes in NOD mice.
Keywords
Animals, Cell Death, Cell Line, Cells, Cultured, Cytokines/genetics, Female, Gene Expression Profiling, Genes, Reporter, Humans, Inflammation/genetics, Inflammation/physiopathology, Insulin-Secreting Cells/cytology, Insulin-Secreting Cells/physiology, Luciferases/genetics, Lymphocytes/cytology, Lymphocytes/immunology, Mice, Mice, Inbred NOD, MicroRNAs/genetics, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Yes
Create date
12/03/2010 14:39
Last modification date
20/08/2019 15:35
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