JQ1 Inhibits the Hyperproliferation and Aggressiveness of Fibroblast‐Like Synoviocytes in Rheumatoid Arthritis via Regulating IL7R
Lin Hong, Tingting Chen, Yuchen Jiang, Xiaohua ZhangABSTRACT
Background
Rheumatoid arthritis (RA) is a chronic autoimmune bone disease. BRD4 is implicated in the pathogenesis of bone disorders. This study aimed to investigate the effects of a BRD4 inhibitor JQ1 on RA.
Methods
Fibroblast‐like synoviocytes (FLS) were exposed to TNF‐α to establish an in vitro RA model. mRNA levels were detected using RT‐qPCR. Protein expression was assessed by Western blot. The behaviors of FLS were analyzed using CCK‐8, EdU, wound scratch, and transwell assays.
Results
We found that LPS exposure promoted an inflammatory response in FLS, as well as mediated cell proliferation and migration. Interestingly, JQ1 inhibited the inflammatory response and the morbidity of FLS. Mechanistically, targeting BRD4 by JQ1 inhibited acetylation modification for H3K27 on IL7R promoter, downregulating the expression of IL7R. However, IL7R overexpression reversed the effects of JQ1 and promoted the inflammatory response and the morbidity of FLS.
Conclusion
JQ1 inhibits the inflammatory response, proliferation, and migration of RA FLS via downregulating IL7R. Therefore, JQ1 exerts protective effects on RA.