Immunoglobulin G4-related sialadenitis (IgG4-RS) is a chronic fibro-inflammatory disease characterized by glandular fibrosis and hyposalivation. Here we aimed to explore the role of cellular senescence in the pathogenesis of IgG4-RS-related fibrosis.
The expression of senescence markers and proinflammatory cytokines in the submandibular glands (SMGs) of IgG4-RS patients (n = 18) and controls (n = 14) was determined by proteomics, real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry. After interleukin-4 (IL-4) treatment, high-throughput RNA-sequencing was performed to identify the differentially expressed genes in SMG-C6 cells. A glandular fibrosis model was established by the intraglandular injection of IL-4 into mouse SMGs (n = 8 per group).
Salivary acinar and ductal epithelial cells underwent senescence in IgG4-RS patients, as indicated by the elevated activity of senescence-associated β-galactosidase, lipofuscin accumulation, enhanced expression of senescence markers (p53 and p16
The cellular senescence induced by IL-4 through the ROS-p38 MAPK-p16