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.

Grieco, F.A., Sebastiani, G., Juan Mateu, J., Villate, O., Marroqui, L., Ladrière, L., et al. (2017). 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. DIABETES, 66(1), 100-112 [10.2337/db16-0592].

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;DOTTA, FRANCESCO;
2017-01-01

Abstract

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.
2017
Grieco, F.A., Sebastiani, G., Juan Mateu, J., Villate, O., Marroqui, L., Ladrière, L., et al. (2017). 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. DIABETES, 66(1), 100-112 [10.2337/db16-0592].
File in questo prodotto:
File Dimensione Formato  
2017 Grieco et al Diabetes.pdf

non disponibili

Descrizione: Free full-text sul sito dell'editore e su PubMed Central
Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 2.02 MB
Formato Adobe PDF
2.02 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
DOTTA-MicroRNAs miR-23a-3p-Post-Print.pdf

accesso aperto

Descrizione: Post-Print
Tipologia: Post-print
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 1.5 MB
Formato Adobe PDF
1.5 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1003882