Background Hyperproliferative and invasiveness are the characteristics of fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLSs), which contribute mainly to RA disease progression and ultimately to joint destruction. Endo180 is a recycling endocytic receptor that has functions to regulate cell migration and bind to internalize collagens. However, the expression of Endo180 in RA-FLSs and its underlying mechanisms remain unclear.
Objectives The aim of this study was to examine the expression of Endo180 in RA-FLSs and the role it played in RA pathological process.
Methods Tissues were collected from RA patients with joint replacement surgery or arthroscopy and RA-FLSs were obtained by tissue culture;Westren blotting was used to measure the expression of Endo180 in RA-FLSs. Chemically synthesized small interference RNA (siRNA) specifically targeting Endo180 gene was transfected into RA-FLSs by cationic liposome; The interference efficiency of Endo180-siRNA on the production of Endo180 RNA and protein was determined by RT-qPCR and Western blotting respectly; The proliferative inhibition rate was examined by CCK8 assay and the migration of RA-FLSs were examined by Transwell assay.
Results Expression of Endo180 was obviously higher in fibroblast-like synoviocytes in RA than OA and the traumatic patients. And its expression level has positive correlation with disease activity described as DAS28. The proliferative inhibition rate was obviously higher in the Endo180-siRNA group than the control groups (P<0.05) after transfection for 48h (16.31%±1.17%), 72h (23.53%±2.62%), 96h (18.01%±1.96%). Transwell migration assay demonstrated the RA-FLSs through the transwell membrane in Endo180-siRNA group (21.27±6.35) were lesser than the NC-siRNA group (80.20±11.12) (P<0.05) and the blank control group (82.17±10.36) (P<0.05).
Conclusions Endo180 may play a role in the regulation of proliferation and migration of RA-FLSs, which may provide beneficial therapeutic effects in RA.
Melander MC, Jürgensen HJ, Madsen DH,et al. The collagen receptor uPARAP/Endo180 in tissue degradation and cancer (Review).Int J Oncol. 2015 Oct;47(4):1177–88. doi: 10.3892/ijo.2015.3120. Epub 2015 Aug 12.
Madsen DH, Jurgensen HJ, Ingvarsen S, et al. Endocytic collagen degradation:a novel mechanism involved in protection against liver fibrosis. J Pathol. 2012 May;227(1):94–105. doi: 10.1002/path.3981. Epub 2012 Feb 17.
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.