Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor that can affect cell proliferation, migration, invasion, apoptosis, and other cellular processes. The study aimed to clarify the effect of ELK3 in the biological activity and ferroptosis phenotype of RA fibroblast-like synoviocytes (FLS), and to reveal its molecular mechanism in regulating ferroptosis in RA FLS.
Methods
We investigated the impact of ELK3 on the biological activity and ferroptosis phenotype of RA FLS using real-time quantitative polymerase chain reaction, immunohistochemistry, Transwell assay, CCK-8 assay, and ferroptosis-related indicator kit. The molecular mechanism of ELK3 in RA FLS was further explored using Western blot, chromatin immunoprecipitation polymerase chain reaction, and other experiments.
Results
ELK3 was highly expressed in RA. Silencing ELK3 inhibited the invasion and proliferation of RA FLS (both p < 0.05). After silencing ELK3 in imidazole ketone erastin-induced RA FLS, intracellular reactive oxygen species, lipid peroxidation levels, ferrous ion content, 4-Hydroxynonenal levels, and Malondialdehyde concentrations all increased. Additionally, ELK3 affects ferroptosis in RA FLS by regulating kelch-like ECH-associated protein 1 (p < 0.05).
Conclusions
Silencing ELK3 leads to decreased invasion and proliferation of RA FLS, affecting their biological activity. ELK3 inhibits ferroptosis by suppressing its transcriptional activity through binding to the kelch-like ECH-associated protein 1 promoter. This suggests that ELK3 may be a potential target for RA therapy.
Full text:
https://www.xiahepublishing.com/2472-0712/ERHM-2024-00036
The study was recently published in the Exploratory Research and Hypothesis in Medicine .
Exploratory Research and Hypothesis in Medicine (ERHM) publishes original exploratory research articles and state-of-the-art reviews that focus on novel findings and the most recent scientific advances that support new hypotheses in medicine. The journal accepts a wide range of topics, including innovative diagnostic and therapeutic modalities as well as insightful theories related to the practice of medicine. The exploratory research published in ERHM does not necessarily need to be comprehensive and conclusive, but the study design must be solid, the methodologies must be reliable, the results must be true, and the hypothesis must be rational and justifiable with evidence.
