NRIP1 disrupts ERα signal in Sjögren's disease via AQP5 suppression and MYC-driven salivary dysfunction - PubMed
3 hours ago
- #salivary dysfunction
- #Sjögren's disease
- #NRIP1
- NRIP1 is abnormally upregulated in Sjögren's disease (SjD) and disrupts salivary gland function.
- NRIP1 forms a complex with estrogen receptor α (ERα), inhibiting saliva secretion and causing epithelial cell death.
- The NRIP1-ERα complex suppresses aquaporin-5 (AQP5) expression and promotes MYC expression in SjD.
- NRIP1-ERα binds to estrogen response elements on the AQP5 promoter, reducing salivary gland secretion.
- Elevated MYC levels due to NRIP1-ERα binding promote apoptosis and alter immune regulation and cell metabolism in SjD.
- Nrip1-knockout/ovariectomized mice did not develop SjD phenotypes, confirming NRIP1's role in the disease.
- Molecular dynamic simulations show NRIP1 competitively binds to ERα, masking the estradiol (E2) binding site.
- NRIP1 is proposed as a diagnostic parameter and potential therapeutic target for SjD management.