1. Rapamycin suppresses rheumatoid arthritis fibroblast synovial cell proliferation and induces apoptosis via the AKT/mTORC1 pathway
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Shengxiao Zhang, Xiaorong Hu, Qinyi Su, Heyi Zhang, Ting Cheng, Jia Wang, Ruomeng Pei, Xin Li, Ruqi Zhang, Hongfang Shao, Caihong Wang, and Xiaofeng Li
- Subjects
apoptosis ,mTORC1 ,rapamycin ,rheumatoid arthritis ,synovial fibroblasts ,Immunologic diseases. Allergy ,RC581-607 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by the overproliferation of synovial fibroblast‐like synoviocytes (FLSs) in the lining, leading to chronic inflammation and progressive joint damage. RA pathogenesis involves lymphocyte infiltration, increased synovial cell proliferation, and impaired cell death. This study investigated the effects of rapamycin on RA‐FLSs and explored the underlying molecular mechanisms. Methods The optimal drug concentration and time for rapamycin administration were determined using a cell counting kit‐8 assay. The concentration of rapamycin varied from 1 to 25 nmol/L. The mRNA expression levels of protein kinase B (AKT), mammalian target of rapamycin (mTOR), B cell lymphoma 2 (Bcl‐2), and Bcl‐2‐associated X protein (Bax) were quantified by real‐time polymerase chain reaction. Protein expression (p‐AKT, AKT, p‐mTOR, mTOR, pS6 kinase [S6K], S6K, p‐4E‐binding protein 1 [4EBP1], 4EBP1, Bcl‐2, Bax, caspase 3, caspase 9, cyclin‐dependent kinase 2 [CDK2], and CD1) were detected by Western blotting analysis. Results Rapamycin suppresses RA‐FLS proliferation and induces apoptosis in a dose‐dependent manner. Rapamycin significantly elevated the protein expression of Bax (p
- Published
- 2024
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