Exploring the Molecular Mechanisms of the Involvement of GZMB-Caspase-3-GSDME Pathway in the Progression of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenesis. Granzyme B (GZMB) has been reported as a potential therapeutic target for RA treatment, but its mechanism remains unclear. This study aimed to explore the molecular mechanism of the GZMB-Caspase-3-GSDME pathway in the progression of RA. An SD rat model of RA was constructed, and Western blot analysis was used to verify the high expression of the GZMB gene in RA rats. Functional validation was then performed on two common RA cells, HFLS-RA cells and MH7A cells, by inhibiting the GZMB gene with the GZMB siRNA virus. Cell proliferation function was measured by CCK8 and EDU assays; cell pyroptosis markers were detected by the LDH assay; inflammation factor levels were measured by ELISA; and the expression of GZMB and pathway-related genes and proteins was measured by Western blot. After GZMB silencing, cell proliferation was decreased compared to the control group, and the inflammation factors IL-1b and IL-18, as well as the pyroptosis markers LDH, IL-1b, and IL-18, were all reduced. The GZMB-related proteins GZMB, caspase-3, and Gasdermin E (GSDME) were also decreased. Therefore, GZMB silencing reduces pyroptosis by inhibiting caspase-3 and Gasdermin E decomposition. In summary, GZMB silencing inhibits the activation of caspase-3 and Gasdermin E, thereby delaying inflammation in RA. The GZMB gene may be a potential therapeutic target for RA. •GZMB (Granzyme B) has been identified as a potential therapeutic target for the treatment of Rheumatoid arthritis (RA).•This study aimed to explore the molecular mechanism of the GZMB-Caspase3-GSDME pathway in the progression of RA using an SD rat model and RA cells.•GZMB silencing reduced cell proliferation and the levels of inflammation factors and pyroptosis markers, indicating that it delays inflammation in RA.•GZMB silencing inhibits the activation of caspase3 and Gasdermin E, suggesting that the GZMB gene may be a potential therapeutic target for RA.•This study provides insights into the molecular mechanism underlying the progression of RA and suggests a potential new avenue for its treatment.