1. Paeonol suppresses fibroblast synovitis by increasing MANF expression
Yu-Bao SHAO ; Xiao-Yu CHEN ; Lan-Xin BAO ; Tao-Rong WANG ; Xiao-Yu CHEN ; Wen-Hao LI ; Wen-Hart ZHOU ; Jin-Chen DAI ; Meng-Meng CHEN ; Jing YE ; Da-Hai ZHAO
Chinese Pharmacological Bulletin 2021;37(7):958-964
Aim To investigate the possible mechanism of paeonol inhibiting the inflammatory response of fibroblast synovial cells (RA-FLSS) in rheumatoid arthritis. Methods CCK-8 assay was used to detect Paeonol's inhibitory level on the abnormal proliferation of arthritis human fibroblast synovial cells (RA-FLSs). The levels of endoplasmic reticulum stress-related proteins MANF and ATF6 were detected by Western blot. Cell localization of transcription factor p65 and Mesencephalic Astrocyte Derived Neurotrophic Factor (MANF) was detected by immunofluorescence. RT-qPCR detected the changes of p65 target genes. Results Paeonol could significantly inhibit the abnormal proliferation of RA-FLSS cells. Paeonol activates ATF6 and increases the expression of MANF. Paeonol promoted the nuclear transfer of MANF protein and inhibited the transcriptional activity of p65. Conclusion Paeonol promotes the expression of MANF and nuclear transfer through the endoplasmic reticulum stress pathway and affects the progression of RA by inhibiting the transcriptional activity of p65.
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