Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=31823770&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
1,25-(OH)(2)D(3)/Vitamin D receptor alleviates systemic lupus erythematosus by downregulating Skp2 and upregulating p27 #MMPMID31823770
Liu D; Fang YX; Wu X; Tan W; Zhou W; Zhang Y; Liu YQ; Li GQ
Cell Commun Signal 2019[Dec]; 17 (1): 163 PMID31823770show ga
BACKGROUND: Recent evidence has suggested that the 1,25(OH)(2)D(3)/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)(2)D(3)/VDR influences SLE through regulating the Skp2/p27 signaling pathway. METHODS: Initially, the levels of 1,25(OH)(2)D(3), 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)(2)D(3) supplement. In addition, the distribution of splenic immune cells was observed in these mice. RESULTS: Among the SLE patients, the levels of 1,25(OH)(2)D(3), 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)(2)D(3)/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)(2)D(3) or VDR reduced the degree of the inflammatory response while acting to regulate the distribution of splenic immune cells. CONCLUSION: This study indicated that 1,25-(OH)(2)D(3)/VDR facilitated the recovery of SLE by downregulating Skp2 and upregulating p27 expression, suggesting the potential of 1,25-(OH)(2)D(3)/VDR as a promising target for SLE treatment.
free
free
free
Cell+Commun+Signal 2019 ; 17 (1): 163
