The Role of NF-κB Signaling Pathway in Lacrimal Gland Damage in Primary Sjögren’s Syndrome: an in vivo study

ABSTRACT: Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammation and damage to exocrine glands, leading to symptoms such as dry eye and reduced tear production. The NF-κB signaling pathway plays a critical role in the inflammatory processes underlying pSS. The aims of the present in vivo study were to investigate the role of NF-κB signaling in lacrimal gland damage and tear secretion in the NOD/Ltj mouse, and to explore the therapeutic potential of NF-κB inhibition. The animal model was established using NOD/Ltj mouse and lacrimal gland pathological change was showed by H&E. Bioinformatics analysis was conducted through RNA sequencing (RNA-seq) and confirmed by RT-qPCR and Western blot. The NOD/Ltj mouse were treated with NF-κB inhibitor JSH-23. Tear secretion assays, ELISA, TUNEL staining, immunofluorescence, immunohistochemistry, and flow cytometry were employed to assess the role of NF-κB signaling in tear production, inflammatory cytokine expression, cell apoptosis, differentially expressed genes (DEGs), and cell differentiation in lacrimal gland damage in pSS mouse. NF-κB signaling was significantly activated in NOD/Ltj mouse lacrimal gland and pSS-related dry eye. NF-κB blockage decreased cell apoptosis, reduced inflammatory cytokine expression, and inhibited Th17 cell differentiation in NOD/Ltj mouse lacrimal glands, as well as restored tear production and normalized the expression of DEGs CARD14 and CCL19. NF-κB signaling played a pivotal role in lacrimal gland damage in pSS model NOD/Ltj mouse by involvement of cell apoptosis, inflammatory cytokine expression and Th17 cell differentiation. Targeting NF-κB signaling may offer a promising therapeutic approach for managing pSS-related dry eye.

ORGANISM(S): Mus musculus

PROVIDER: GSE306385 | GEO | 2025/08/25

REPOSITORIES: GEO