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• W1984607812 endingPage "1146" @default.
• W1984607812 startingPage "1141" @default.
• W1984607812 abstract "Thioredoxin-interacting protein (TXNIP) regulates the redox potential of cells and has previously been found to be upregulated in diabetic states. In a new study, Anath Shalev and colleagues show that TXNIP upregulates the expression of miR-204, which in turn downregulates the expression of MAFA, a key transcription factor regulating insulin expression. These results could further explain the progression of diabetes. Beta-cell dysfunction and impaired insulin production are hallmarks of diabetes1, but despite the growing diabetes epidemic, the molecular mechanisms underlying this disease have remained unclear. We identified thioredoxin-interacting protein (TXNIP), a cellular redox regulator, as a crucial factor in beta-cell biology and show that beta-cell TXNIP is upregulated in diabetes, whereas TXNIP deficiency protects against diabetes by preventing beta-cell apoptosis2,3. Here we show that TXNIP and diabetes induce beta-cell expression of a specific microRNA, miR-204, which in turn blocks insulin production by directly targeting and downregulating MAFA, a known insulin transcription factor. In particular, we first discovered the regulation of miR-204 by TXNIP by microarray analysis, followed by validation studies in INS-1 beta cells, islets of Txnip-deficient mice, diabetic mouse models and primary human islets. We then further found that TXNIP induces miR-204 by inhibiting the activity of signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in miR-204 regulation4,5. We also identified MAFA as a target that is downregulated by miR-204. Taken together, our results demonstrate that TXNIP controls microRNA expression and insulin production and that miR-204 is involved in beta-cell function. The newly identified TXNIP–miR-204–MAFA–insulin pathway may contribute to diabetes progression and provides new insight into TXNIP function and microRNA biology in health and disease." @default.
• W1984607812 created "2016-06-24" @default.
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• W1984607812 date "2013-08-25" @default.
• W1984607812 modified "2023-10-11" @default.
• W1984607812 title "Thioredoxin-interacting protein regulates insulin transcription through microRNA-204" @default.
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• W1984607812 doi "https://doi.org/10.1038/nm.3287" @default.
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