Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome.
Recent clinical and experimental evidence suggests that endoplasmic reticulum (ER) stress contributes to the life-and-death decisions of β cells during the progression of type 1 and type 2 diabetes. Although crosstalk between inflammation and ER stress has been suggested to play a significant role in β cell dysfunction and death, a key molecule connecting ER stress to inflammation has not been identified. Here we report that thioredoxin-interacting protein (TXNIP) is a critical signaling node that links ER stress and inflammation. TXNIP is induced by ER stress through the PERK and IRE1 pathways, induces IL-1β mRNA transcription, activates IL-1β production by the NLRP3 inflammasome, and mediates ER stress-mediated β cell death. Collectively, our results suggest that TXNIP is a potential therapeutic target for diabetes and ER stress-related human diseases such as Wolfram syndrome.
Duke Scholars
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- eIF-2 Kinase
- Thioredoxins
- Signal Transduction
- Protein Serine-Threonine Kinases
- NLR Family, Pyrin Domain-Containing 3 Protein
- Mice, Knockout
- Mice
- Membrane Proteins
- Luciferases
- Interleukin-1beta
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- eIF-2 Kinase
- Thioredoxins
- Signal Transduction
- Protein Serine-Threonine Kinases
- NLR Family, Pyrin Domain-Containing 3 Protein
- Mice, Knockout
- Mice
- Membrane Proteins
- Luciferases
- Interleukin-1beta