Endophilin A2, a Potential Therapeutic Target for Lupus, Promotes Lupus Progression
Lu‐Qi Yang, You‐Yu Lan, You‐Qiang Wang, Si‐Yu Feng, An‐Fang Huang, Wang‐Dong XuABSTRACT
Objective
Endophilin A2 (EPA2) is a member of the Endophilin family. The relationship between EPA2 and SLE pathogenesis is unclear.
Methods
Plasma levels of EPA2 in SLE patients and healthy controls were detected by ELISA, and EPA2 mRNA levels of SLE patients were explored by qRT‐PCR. EPA2 siRNA adenovirus was further injected into pristane‐induced lupus mice, and the histological and serological changes were observed. In vitro, EPA2 siRNA adenovirus was transfected to human umbilical vein endothelial cells (HUVECs) in the presence of growth differentiation factor 15 (GDF15), and the proliferation, migration, and tube‐forming ability of HUVECs were discussed.
Results
Plasma EPA2 levels were significantly higher in SLE patients than in healthy controls (p < 0.001), and EPA2 mRNA levels were significantly higher in SLE patients than in healthy controls as well (p = 0.030). Lupus mice exhibited splenomegaly, severe histologic damage, and high levels of autoantibodies (antinuclear antibody (ANA), anti‐double‐stranded DNA antibody (anti‐dsDNA), and immunoglobulin G (IgG)) (vs. the control group, all p < 0.05). After injection of EPA2 siRNA adenoviruses, the lupus mice showed a lower proportion of CD11b+LY‐6C+, F4/80+, CD11c+, CD19+, CD8+, Th1+, Th2+, Th17+ cells and reduced expression of pro‐inflammatory cytokines, and autoantibodies (vs. the adenoviral empty vector group, all p < 0.05). Addition of EPA2 siRNA adenovirus to HUVECs resulted in decreased GDF15 mRNA levels and reduced cell proliferation, migration and tube formation. However, in the presence of GDF15, EPA2‐mediated effects were reversed, and the proliferation, migration, and tube formation ability of HUVECs were enhanced.
Conclusion
EPA2 may regulate angiogenesis through GDF15, and then involve in SLE pathogenesis.