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Virus-like infection induces human β cell dedifferentiation.
JCI insight 3:97732 (2018)
Type 1 diabetes (T1D) is a chronic disease characterized by an autoimmune-mediated destruction of insulin-producing pancreatic β cells. Environmental factors such as viruses play an important role in the onset of T1D and interact with predisposing genes. Recent data suggest that viral infection of human islets leads to a decrease in insulin production rather than β cell death, suggesting loss of β cell identity. We undertook this study to examine whether viral infection could induce human β cell dedifferentiation. Using the functional human β cell line EndoC-βH1, we demonstrate that polyinosinic-polycytidylic acid (PolyI:C), a synthetic double-stranded RNA that mimics a byproduct of viral replication, induces a decrease in β cell-specific gene expression. In parallel with this loss, the expression of progenitor-like genes such as SOX9 was activated following PolyI:C treatment or enteroviral infection. SOX9 was induced by the NF-κB pathway and also in a paracrine non-cell-autonomous fashion through the secretion of IFN-α. Lastly, we identified SOX9 targets in human β cells as potentially new markers of dedifferentiation in T1D. These findings reveal that inflammatory signaling has clear implications in human β cell dedifferentiation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Beta Cells ; Diabetes ; Inflammation ; Nf-kappab ; Virology
ISSN (print) / ISBN
2379-3708
e-ISSN
2379-3708
Journal
JCI insight
Quellenangaben
Volume: 3,
Issue: 3,
Article Number: 97732
Publisher
Clarivate
Publishing Place
Ann Arbor, Michigan
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)