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Impaired upregulation of Stat2 gene restrictive to pancreatic β-cells is responsible for virus-induced diabetes in DBA/2 mice.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Jan 22; Vol. 521 (4), pp. 853-860. Date of Electronic Publication: 2019 Nov 07. - Publication Year :
- 2020
-
Abstract
- Viral infection is a putative causal factor for the development of type 1 diabetes, but the exact pathogenic mechanism of virus-induced diabetes (VID) remains unclear. Here, to identify the critical factors that regulate VID, we analyzed encephalomyocarditis D (EMC-D) VID-sensitive DBA/2 mice in comparison with resistant B6 mice. EMC-D virus-induced cell death occurred more frequently in DBA/2 β-cells than in B6 β-cells with 100U/ml IFN-β priming in vitro. We therefore purified β-cells using flow cytometry from mice two days after EMC-D virus infection and subjected them to microarray analysis. As a results, innate immune response pathway was found to be enriched in B6 β-cells. The signal transducer and activator of transcription 2 (Stat2) gene interacted with genes in the pathway. Stat2 gene expression levels were lower in DBA/2 mice than in B6 mice, restrictive to β-cells. Moreover, administration of IFN-β failed to upregulate Stat2 gene in DBA/2 β-cells than in those of B6 in vivo. The viral titer significantly increased only in the DBA/2 pancreas. Thus, these provided data suggest that impaired upregulation of Stat2 gene restrictive to β-cells at the early stage of infection is responsible for VID development in DBA/2 mice.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cardiovirus Infections drug therapy
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental virology
Diabetes Mellitus, Type 1 genetics
Encephalomyocarditis virus
Gene Expression Regulation
Immunity, Innate genetics
Insulin-Secreting Cells drug effects
Insulin-Secreting Cells immunology
Interferon Type I pharmacology
Male
Mice, Inbred C57BL
Mice, Inbred DBA
STAT2 Transcription Factor metabolism
Up-Regulation
Cardiovirus Infections complications
Diabetes Mellitus, Type 1 virology
Insulin-Secreting Cells virology
STAT2 Transcription Factor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 521
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 31708097
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.10.193