Background RICTOR (rapamycin-insensitive companion of mTOR) is a key component of mTORC2 (mammalian target of rapamycin complex 2), which can regulate the organization of actin cytoskeleton and phosphorylate/activate Akt. Akt signaling is activated in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and plays an important role in the pathogenesis of RA. We hypothesized that RICTOR might be involved in the long-lasting changed phenotype of RA-FLS.
Objectives To investigate the expression of RICTOR in RA-FLS.
Methods FLS were isolated from the primary synovial tissues, which were obtained during joint replacement surgery or arthroscopy from seven patients with RA, four patients with osteoarthritis (OA), and four patients with joint trauma (Trauma group). The expression of RICTOR in FLS from the three groups was evaluated at the protein level by western blotting and at the mRNA level by Real-time PCR. Three of the RA-FLS samples were selected randomly for being treated with 10ng/ml TNF-alpha, 4nM Akt pathway blocker MK-2206 with or without 10ng/ml TNF-alpha. The expression of RICTOR was detected by western blotting after 24h.
Results 1) Western blotting and Realtime-PCR showed that the expression of RICTOR was elevated in RA-FLS compared with that in Trauma-FLS (both p<0.05) at protein and mRNA level. But no difference was found between RA-FLS and OA-FLS. 2) Compared with the control group, treatment with MK-2206 (with or without TNF-alpha) for 24h decreased the expression of RICTOR protein (both p<0.01), while the expression of RICTOR in RA-FLS was not influenced by stimulation with TNF-alpha.
Conclusions Expression of RICTOR is elevated in RA-FLS in vitro. The increase is due to the activation of Akt signaling. The results suggest that RICTOR may contribute to the stable activation of RA-FLS.
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Disclosure of Interest None Declared
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