RND1 Induces Ferroptosis to Alleviate Inflammatory Response, Proliferation, Invasion, and Migration of Rheumatoid Synoviocytes.

Abstract

Background: Ferroptosis is involved in the occurrence and development of inflammatory arthritis. RND1 has been reported to possess pro-ferroptosis activity.

Objective: This study was designed to explore the role and the molecular mechanism of RND1 in rheumatoid arthritis (RA).

Methods: DBA/1 mice were exposed to type II collagen immunization. The pathological damage of the knee joints of mice was observed with H&E staining and RND1 expression in synovial tissues was detected using Western blot. In vitro, Western blot was used to measure RND1, ferroptosis-, migration- and inflammation-related proteins. The cell proliferation, migration and invasion were detected using CCK-8 method, EdU staining, wound healing and transwell assays. The levels of inflammatory factors were detected with ELISA and RT-qPCR. Relative iron level, GSH and MDA concentrations were detected with corresponding assay kits. BODIPY 581/591 C11 kit measured lipid ROS. 4-HNE and GPX4 expression were detected using immunofluorescence assay.

Results: This study found that RND1 expression was reduced in the synovial tissues of RA mice and human fibroblast-like MH7A synoviocytes. It was also found that the upregulation of RND1 inhibited the proliferation, migration, invasion and inflammatory response in rheumatoid synovial cells via ferroptosis.

Conclusion: Collectively, RND1 exerted protective impacts on RA, which might be mediated by ferroptosis.