Deleting Mitochondrial Superoxide Dismutase 2 in Salivary Gland Ductal Epithelial Cells Recapitulates Non-Sjögren's Sicca Syndrome.
Int J Mol Sci
; 25(11)2024 May 30.
Article
in En
| MEDLINE
| ID: mdl-38892170
ABSTRACT
Elevated oxidative stress can play a pivotal role in autoimmune diseases by exacerbating inflammatory responses and tissue damage. In Sjögren's disease (SjD), the contribution of oxidative stress in the disease pathogenesis remains unclear. To address this question, we created mice with a tamoxifen-inducible conditional knockout (KO) of a critical antioxidant enzyme, superoxide dismutase 2 (Sod2), in the salivary glands (i-sg-Sod2 KO mice). Following tamoxifen treatment, Sod2 deletion occurred primarily in the ductal epithelium, and the salivary glands showed a significant downregulation of Sod2 expression. At twelve weeks post-treatment, salivary glands from the i-sg-Sod2 KO mice exhibited increased 3-Nitrotyrosine staining. Bulk RNA-seq revealed alterations in gene expression pathways related to ribosome biogenesis, mitochondrial function, and oxidative phosphorylation. Significant changes were noted in genes characteristic of salivary gland ionocytes. The i-sg-Sod2 KO mice developed reversible glandular hypofunction. However, this functional loss was not accompanied by glandular lymphocytic foci or circulating anti-nuclear antibodies. These data demonstrate that although localized oxidative stress in salivary gland ductal cells was insufficient for SjD development, it induced glandular dysfunction. The i-sg-Sod2 KO mouse resembles patients classified as non-Sjögren's sicca and will be a valuable model for deciphering oxidative-stress-mediated glandular dysfunction and recovery mechanisms.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Salivary Glands
/
Superoxide Dismutase
/
Sjogren's Syndrome
/
Mice, Knockout
/
Oxidative Stress
/
Epithelial Cells
/
Mitochondria
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Publication country:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND