1,25-(OH)2D3/Vitamin D receptor alleviates systemic lupus erythematosus by downregulating Skp2 and upregulating p27

Abstract Background 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. 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. Methods Initially, 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. Results Among 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. Conclusion This 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.

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Serum vitamin D/25(OH)D associated with toll-like receptor (TLR) 2 expression of immune cells in the saliva of Systemic Lupus Erythematosus: a preliminary study

Journal of Oral Medicine and Oral Surgery ◽

10.1051/mbcb/2020062 ◽

2021 ◽

Vol 27 (2) ◽

pp. 22

Author(s):

Hendri Susanto ◽

Bagus Soebadi ◽

Diah Savitri Ernawati ◽

Adiastuti Endah Pamardiati ◽

Hening Tuti Hendarti ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Immune Cells ◽

Lupus Erythematosus ◽

Serum Vitamin ◽

Toll Like Receptor ◽

Systemic Lupus ◽

Tlr2 Expression ◽

Cross Sectional ◽

Serum Vitamin D

Objective: Vitamin D deficiency may contribute to Systemic Lupus Erythematosus (SLE) development. Vitamin D may involve in pathogen recognition through Toll-like receptor (TLR) 2 in immune cells in saliva. This study aimed to determine the correlation between serum vitamin D/25(OH)D and TLR2 expression of immune cells in the saliva of SLE. Materials and methods: This cross-sectional study conducted at the the SLE patients who met the inclusion and exclusion criteria. Those who had signed informed consent involved to underwent unstimulated saliva collection and blood samples for TLR2 and vitamin D/25(OH)D examination. The correlation between serum vitamin D/25(OH)D concentration and salivary TLR2 expression was analyzed using the correlation test, linear regression with 95% confidence level. Results: Thirty SLE patients had a mean serum vitamin D/25(OH)D concentration of 9.98 ± 4.64 ng/ml. The mean of TLR2 expression of CD11b+ cells in saliva was 26.03 ± 20.92%. There was a significant positive correlation between serum vitamin D/25(OH)D concentration and TLR 2 expression of CD11b+ cells in the saliva. (r = 0.434; P < 0.05). Vitamin D/25(OH)D was the only predictor for TLR 2 expression. Conclusion: Serum vitamin D/25(OH)D concentrations associated with TLR2 expression of CD11b+ cells in the saliva of SLE.

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Impact of the polymorphism in vitamin D receptor gene BsmI and the risk of systemic lupus erythematosus

Clinical Rheumatology ◽

10.1007/s10067-016-3206-0 ◽

2016 ◽

Vol 35 (4) ◽

pp. 1121-1121

Author(s):

Linhui Li ◽

Bin Yang ◽

Lanlan Wang

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Vitamin D Receptor ◽

Lupus Erythematosus ◽

Receptor Gene ◽

Vitamin D Receptor Gene ◽

Systemic Lupus

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Vitamin D receptor (VDR) gene polymorphisms and susceptibility to systemic lupus erythematosus clinical manifestations

Lupus ◽

10.1177/0961203313500549 ◽

2013 ◽

Vol 22 (11) ◽

pp. 1110-1117 ◽

Cited By ~ 18

Author(s):

J de Azevêdo Silva ◽

K Monteiro Fernandes ◽

JA Trés Pancotto ◽

T Sotero Fragoso ◽

EA Donadi ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Vitamin D Receptor ◽

Lupus Erythematosus ◽

Gene Polymorphisms ◽

Clinical Manifestations ◽

Systemic Lupus ◽

Vdr Gene ◽

Vdr Gene Polymorphisms

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Vitamin D receptor gene polymorphism Fok I in the Polish population does not contribute to the risk of systemic lupus erythematosus

Lupus ◽

10.1177/0961203313482743 ◽

2013 ◽

Vol 22 (7) ◽

pp. 750-751 ◽

Cited By ~ 6

Author(s):

J Bogaczewicz ◽

B Kaleta ◽

A Sysa-Jedrzejowska ◽

E Robak ◽

J Lukaszkiewicz ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Gene Polymorphism ◽

Vitamin D Receptor ◽

Lupus Erythematosus ◽

Receptor Gene ◽

Vitamin D Receptor Gene ◽

Polish Population ◽

Systemic Lupus ◽

Receptor Gene Polymorphism

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Impact of vitamin D receptor gene polymorphism on Systemic Lupus Erythematosus susceptibility: A pooled analysis

10.21203/rs.2.15551/v1 ◽

2019 ◽

Author(s):

Shi-kun Yang ◽

Na Liu ◽

Ying-qiu Zhu ◽

Wei-juan Zhang ◽

Na Song ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Gene Polymorphism ◽

Vitamin D Receptor ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Receptor Gene ◽

Systemic Lupus ◽

Vdr Gene ◽

Apai Polymorphism

Abstract It is still unclear whether there was an association between vitamin D receptor (VDR) gene polymorphism and systemic lupus erythematosus (SLE). This meta analysis including 19 studies were performed using Stata software. In our analysis, VDR ApaI polymorphism was correlated with SLE susceptibility in general populations (AA vs aa: P=0.003; AA+Aa vs aa: P=0.000). VDR gene ApaI and BsmI polymorphism were correlated with SLE susceptibility in Caucasian populations (BB vs Bb+bb: p=0.005; B vs b: P=0.026; AA vs aa: P =0.038). VDR BsmI and FokI polymorphism were correlated with SLE in African populations (BB+Bb vs bb: P=0.000; FF vs Ff +ff: P=0.000; F vs f: P=0.000; FF vs ff: P=0.000; FF+Ff vs ff: P=0.000). VDR ApaI polymorphism was correlated with SLE in Asian populations (AA+Aa vs aa) when stratified by race. Additionly, ApaI polymorphism was correlated with SLE in female subjects (AA vs aa: P =0.022) when stratified by gender. But there was no association between VDR TaqI polymorphism and SLE susceptibility in our analysis.

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