Increased expression of calreticulin promotes angiogenesis involved in the pathogenesis of rheumatoid arthritis / 天津医药

ABSTRACT

Objective Calreticulin (CRT)is a multifunctional protein of endoplasmic reticulum implicated in the pathogenesis of rheumatoid arthritis(RA). The present study was undertaken to determine whether CRT was involved in an?giogenesis events in RA. Methods Serum CRT levels were measured by enzyme-linked immnuosorbent assay(ELISA)in 106 patients with established RA, 75 osteoarthritis(OA)and 80 healthy controls(HC). CRT levels in synovial fluid were al?so measured in 25 RA and 22 OA patients. The expression of CRT in synovial tissue was examined by immunohistology. In order to investigate the role of CRT on angiogenesis, human umbilical vein endothelial cells(HUVECs)were isolated and cultured for in vitro experiments. The proliferation, migration and tube formation of HUVECs following CRT stimulation were examined in vitro by MTT assay, scratch wound healing assay and tube formation assay. Results Our results showed a sig?nificantly higher concentration of CRT in serum [(6.4±3.1) μg/L] of RA patients compared to that of OA [(3.7±0.9) μg/L, P<0.01] and HC [(3.4±1.0) μg/L, P<0.01];and significantly higher CRT in synovial fluid [(6.9±3.4) μg/L] of RA vs OA [(3.9± 0.7) μg/L, P<0.01]. Increased CRT expression predominantly localized to vascular endothelial cells, inflammatory cells and perivascular areas in both the lining and sublining layers of RA synovial tissue. Furthermore, CRT significantly promoted the proliferation, migration and tube formation of HUVECs, as showed by MTT assay, scratch wound healing assay and tube for?mation assay. Conclusion These findings suggested that CRT may be involved in synovitis and pannus formation events via promoting angiogenesis in RA.