Overexpression of Aquaporin 1 in Synovium Aggravates Rat Collagen-Induced Arthritis Through Regulating -Catenin Signaling: An in vivo and in vitro Study

Introduction: Previous studies have confirmed that aquaporin 1 (AQP1) is up-regulated in synovium of rheumatoid arthritis (RA), but its exact pathogenic mechanisms in RA are unclear. This study revealed the pathogenic role of AQP1 in rat collagen-induced arthritis (CIA) and the underlying mechanisms related to beta-catenin signaling. Materials and Methods: Secondary paw swelling and pathological changes of ankle joints were used to evaluate the severity of rat CIA. Synovial AQP1 and beta-catenin expression were measured by immunohistochemistry (IHC) and Western blot assay. AQP1 siRNA was applied to knockdown AQP1 in cultured CIA fibroblast-like synoviocyte (FLS). Assays of MTT, PCNA immunofluorescence and transwell were performed to detect cell proliferation, migration and invasion. The protein levels of beta-catenin pathway members and ratio of TOP/FOP luciferase activity were also measured. Results: In vivo, we revealed that synovial AQP1 and beta-catenin expressions in CIA rats were higher than normal rats, and synovial AQP1 expression of CIA rats increased in parallel with secondary paw swelling and total pathological score on joint damage. Correlation analysis of IHC results indicated that synovial AQP1 expression positively correlated with beta-catenin expression in CIA rat. In vitro, AQP1 siRNA apparently reduced the proliferation, migration and invasion of CIA FLS by inhibiting beta-catenin signaling pathway. As an activator of beta-catenin signaling, lithium chloride (an inhibitor of GSK-3 beta) reversed the inhibitory effects of AQP1 siRNA on the cultured CIA FLS. Conclusion: We concluded that the overexpression of synovial AQP1 aggravated rat CIA by promoting the activation of FLS through beta-catenin signaling pathway.