Nuclear factor-erythroid 2-related 2 mRNA and protein are highly expressed in the synovium of patients with rheumatoid arthritis

Abstract

Introduction: Nuclear factor-erythroid 2-related factor 2 (Nrf2) is the main transcription factor for antioxidant stress response. The aim of this study was to analyze the expression level of Nrf2 mRNA and protein in the synovium of patients with rheumatoid arthritis (RA), and the association between Nrf2 mRNA and oxidative stress. Materials and Methods: The synovia harvested from 41 patients with RA served as the study group and 4 cases with knee osteoarthritis (OA) were registered as the control group. The Nrf2 mRNA expression level was evaluated using real-time polymerase chain reaction (PCR) and the Nrf2 protein via immunohistochemistry. The immunopositivity of the Nrf2 protein was then graded into four stages (none, slight, moderate, and strong) during microscopic examination. In addition, d-reactive oxygen metabolites (d-ROM) measurement was performed using the sera of patients with RA. Results: The expression level of Nrf2 mRNA in the RA synovia (2.34±0.86) was significantly higher than that in the OA synovia (1.5±0.49). The OA synovia had neither moderate nor strong intensity of Nrf2 protein immunopositivity. In the RA synovia, moderate and strong intensities were noted in 23 and three cases, respectively. The immunoreactivity of the Nrf2 protein in the RA synovia was significantly stronger than that in the OA synovia. The Nrf2 mRNA showed significantly correlation with preoperative d-ROM. Conclusion: The present study demonstrated increased upregulation of Nrf2 in the RA synovia compared to that in the OA synovia both at the mRNA expression and protein levels. An increased expression of Nrf2 mRNA may reflect an upregulation of the antioxidant capacity in response to high oxidative stresses.