Background Fibroblast-like synoviocytes (FLS), with some tumor-like characters, play a key role in the pathogenesis of rheumatoid arthritis (RA) . Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene, and its mRNA expression has been reported to be absent in the lining layer of RA synovium, which is supposed to contribute to the invasive behavior of RA-FLSs [2,3]. It has been demonstrated in various kinds of tumor cells that the PTEN protein is a negative regulator of the PI3K/Akt signal pathway . However, data of the PTEN protein level in RA-FLSs and its effect on the phosphorylation status of Akt (Thr308) is limited.
Objectives To investigate the expression of PTEN gene in cultured human RA-FLSs and its effect on Akt (Thr308) phosphorylation status.
Methods FLSs were isolated from synovial tissues obtained from patients with RA, osteoarthritis (OA) or joint trauma during joint replacement surgery or arthroscopy, and each group contains 3 patients. The mRNA expression of PTEN was detected by RT-qPCR. The protein levels of PTEN, pAkt (Thr308) and total Akt, were measured by western blotting. The phosphorylation status of Akt was determined by protein expression ratio of pAkt (Thr308)/total Akt.
Results The expression of PTEN mRNA was significantly lower in RA-FLSs compared with OA-FLSs and joint trauma-FLSs (P<0.01), while no statistically significant difference was observed between those of OA-FLSs and joint trauma-FLSs (P>0.05). Similarly, the PTEN protein level in RA-FLS was much lower than OA-FLSs and joint trauma-FLSs (P<0.05), and there was no difference between the latter two (P>0.05). Moreover, the phosphorylation level of Akt (Thr308) in RA-FLSs was significantly higher than those in the other two control groups (P<0.01), and that in OA-FLSs was much lower than joint trauma-FLSs (P<0.01).
Conclusions The mRNA and protein expression of PTEN are both decreased in cultured RA-FLSs, suggesting that low expression level of PTEN is conserved in RA-FLSs out of the inflammatory environment in vitro throughout passages. And it may contribute to the increased phosphorylation level of Akt (Thr308).
Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nature reviews Rheumatology. 2013 Jan; 9(1):24–33.
Pap T, Franz JK, Hummel KM, Jeisy E, Gay R, Gay S. Activation of synovial fibroblasts in rheumatoid arthritis: lack of Expression of the tumour suppressor PTEN at sites of invasive growth and destruction. Arthritis research. 2000; 2(1):59–64.
Wang CR, Shiau AL, Chen SY, Lin LL, Tai MH, Shieh GS, et al. Amelioration of collagen-induced arthritis in rats by adenovirus-mediated PTEN gene transfer. Arthritis and rheumatism. 2008 Jun; 58(6):1650–1656.
Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nature reviews Molecular cell biology. 2012 May; 13(5):283–296.
Acknowledgement The research was supported by Guangdong natural science foundation (No. 2014A030313080).
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.