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Cited by 279

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Thioredoxin-interacting protein regulates insulin transcription through microRNA-204

Open access
Xu, Guanlan, Chen, Junqin, Jing, Gu, Shalev, Anath·2013·Nature Medicine
DOI 10.1038/nm.3287
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Abstract

Beta-cell dysfunction and impaired insulin production are hallmarks of diabetes, 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 apoptosis. 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 regulation. 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.

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Metadata

Authors
Xu, G., Chen, J., Jing, G., & Shalev, A.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2013-08-25
Volume
19
Issue
9
Pages
1141-1146
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.3287
OpenAlex
W1984607812
Cited by
279
References
41
FWCI
17.66
Type
journal article
Language
en
Open access
green

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