Abstract
BackgroundRecent evidence has suggested that the 1,25(OH)2D3/Vitamin D receptor (VDR) acts to suppress the immune response associated with systemic lupus erythematosus (SLE), a serious multisystem autoimmune disease. Hence, the aim of the current study was to investigate the mechanism by which 1,25-(OH)2D3/VDR influences SLE through regulating the Skp2/p27 signaling pathway.MethodsInitially, the levels of 1,25(OH)2D3, VDR, Skp2, and p27 were measured in collected renal tissues and peripheral blood. Meanwhile, the levels of inflammatory factors, biochemical indicators (BUN, Cr, anti-nRNP IgG, anti-dsDNA IgG) and urinary protein levels were assayed in in VDRinsert and VDR-knockout mice in response to 1,25(OH)2D3 supplement. In addition, the distribution of splenic immune cells was observed in these mice.ResultsAmong the SLE patients, the levels of 1,25(OH)2D3, VDR and p27 were reduced, while the levels of Skp2 were elevated. In addition, the levels of anti-nRNP IgG and anti-dsDNA IgG were increased, suggesting induction of inflammatory responses. Notably, 1,25(OH)2D3/VDR mice had lower concentrations of BUN and Cr, urinary protein levels, precipitation intensity of the immune complex and complement, as well as the levels of anti-nRNP IgG and anti-dsDNA IgG in SLE mice. Additionally, 1,25(OH)2D3 or VDR reduced the degree of the inflammatory response while acting to regulate the distribution of splenic immune cells.ConclusionThis study indicated that 1,25-(OH)2D3/VDR facilitated the recovery of SLE by downregulating Skp2 and upregulating p27 expression, suggesting the potential of 1,25-(OH)2D3/VDR as a promising target for SLE treatment.
Highlights
Recent evidence has suggested that the 1,25(OH)2D3/Vitamin D receptor (VDR) acts to suppress the immune response associated with systemic lupus erythematosus (SLE), a serious multisystem autoimmune disease
SLE vitamin D receptor (VDR)-insert mice were selected for the purposes of the study to investigate the role of the overexpression of VDR in the alleviation of SLE in mice [21]
The results suggested there to be a lower level of hemoglobin and fewer platelets among SLE patients
Summary
Recent evidence has suggested that the 1,25(OH)2D3/Vitamin D receptor (VDR) acts to suppress the immune response associated with systemic lupus erythematosus (SLE), a serious multisystem autoimmune disease. Deficiencies of p27, a cell cycle inhibitor, reduce the activity and quantity of Tregs, and induce lupus-like abnormalities [13] Both Skp and p27 play vital roles in mediating the migration, proliferation and invasion of tumor cells as well as balancing immune tolerance in the development of autoimmune diseases [12, 14], while 1,25-(OH)2D3 is reported to reduce Skp protein expression in metastatic prostate cancer cells [15]. The central objective of the current study was to investigate the potential role of 1, 25-(OH)2D3/VDR in the progression of SLE by regulating the Skp2/p27 signaling pathways
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