Expression of vitamin D receptor in renal tissue of lupus nephritis and its association with renal injury activity

Abstract

Objective

Vitamin D receptor (VDR) has potent anti-inflammatory activities. VDR gene polymorphism has been linked with systemic lupus erythematosus (SLE). However, its expression in the kidney has not been evaluated. This study aimed to investigate the relationship between VDR expression and renal pathology as well as clinical manifestations in lupus nephritis (LN).

Methods

A total of 20 renal biopsy specimens from 35 patients with LN were classified according to the International Society of Nephrology/Renal Pathology Society 2003 LN-type standards pathological type, and the activity index and chronicity index were determined. Five normal renal tissue samples were obtained from surrounding areas distal to nephronophthisis or renal tumors (>2 cm). The expression of VDR was assessed by immunohistochemistry. The relationships between VDR expression and histological injury index, proteinuria and Systemic Lupus International Collaborating Clinics (SLICC) renal activity scores were analyzed.

Results

As compared to the control group, the expression of VDR in the LN group was lower (p < 0.001) and negatively correlated with activity index (r = –0.548, p = 0.012) but not with chronicity index (r = –0.277, p = 0.236). The expression of VDR in renal tissue was also associated with SLICC renal activity scores (r = –0.470, p = 0.037).

Conclusion

The down-regulation of VDR expression in renal tissues of LN patients was negatively correlated with renal activity and injury severity.

Keywords

Systemic lupus erythematosus lupus nephritis vitamin D receptor renal biopsy immunohistochemistry

Get full access to this article

View all access options for this article.

References

Cervera

Khamashta

Font

et al.

Morbidity and mortality in systemic lupus erythematosus during a 10-year period. Medicine 2003; 82: 299–308.

Cheng

Zhou

Zhao

et al.

Human neutrophil peptide 1-3, a component of the neutrophil extracellular trap, as a potential biomarker of lupus nephritis. Int J Rheum Dis 2015; 18: 533–540.

Yougbare

Boire

Roy

et al.

NCS 613 exhibits anti-inflammatory effects on PBMCs from lupus patients by inhibiting p38 MAPK and NF-kappaB signalling pathways while reducing proinflammatory cytokine production. Can J Physiol Pharmacol 2013; 91: 353–361.

Joshi

Pantalena

Liu

et al.

1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 2011; 31: 3653–3669.

Bogaczewicz

Sysa-Jedrzejowska

Arkuszewska

et al.

Vitamin D status in systemic lupus erythematosus patients and its association with selected clinical and laboratory parameters. Lupus 2012; 21: 477–484.

Breslin

Magee

Wallace

et al.

An evaluation of vitamin D status in individuals with systemic lupus erythematosus. Proc Nutr Soc 2011; 70: 399–407.

Garcia-Carrasco

Mendoza-Pinto

Munguia-Realpozo

et al.

Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus. Lupus 2015; 24: 606–612.

Reynolds

Rosenberg

Smith

et al.

Brief report: Vitamin D deficiency is associated with endothelial dysfunction and increases type I interferon gene expression in a murine model of systemic lupus erythematosus. Arthritis Rheumatol 2016; 68: 2929–2935.

Sun

Mustafi

Cerda

et al.

Lithocholic acid down-regulation of NF-kappaB activity through vitamin D receptor in colonic cancer cells. J Steroid Biochem Mol Biol 2008; 111: 37–40.

10.

Chen

Zhang

et al.

Vitamin D receptor inhibits nuclear factor kappaB activation by interacting with IkappaB kinase beta protein. J Biol Chem 2013; 288: 19450–19458.

11.

Liu

Chen

Golan

et al.

Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis. J Clin Invest 2013; 123: 3983–3996.

12.

Wada

Tanaka

Maeda

et al.

Vitamin D receptor expression is associated with colon cancer in ulcerative colitis. Oncol Rep 2009; 22: 1021–1025.

13.

Zhou

. Vitamin D receptor (VDR) gene polymorphisms and Graves' disease: a meta-analysis. Clin Endocrinol (Oxf) 2009; 70: 938–945.

14.

Cai

Zhang

Xin

et al.

Associations between vitamin D receptor gene polymorphisms and ankylosing spondylitis in Chinese Han population: a case-control study. Osteoporos Int 2016; 27: 2327–2333.

15.

Ozaki

Nomura

Nagahama

et al.

Vitamin-D receptor genotype and renal disorder in Japanese patients with systemic lupus erythematosus. Nephron 2000; 85: 86–91.

16.

Luo

Yang

et al.

Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population. Lupus 2012; 21: 53–59.

17.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.

18.

Gladman

Ibanez

Urowitz

. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288–291.

19.

Petri

Kasitanon

Lee

et al.

Systemic Lupus International Collaborating Clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum 2008; 58: 1784–1788.

20.

Pitashny

Schwartz

Qing

et al.

Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum 2007; 56: 1894–1903.

21.

Sabry

Sheashaa

El-Husseini

et al.

Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its correlation with disease activity. Cytokine 2006; 35: 148–153.

22.

Liu

Tretiakova

Kong

et al.

Expression of vitamin D3 receptor in kidney tumors. Hum Pathol 2006; 37: 1268–1278.

23.

Esdaile

Joseph

MacKenzie

et al.

The benefit of early treatment with immunosuppressive agents in lupus nephritis. J Rheumatol 1994; 21: 2046–2051.

24.

Illei

Tackey

Lapteva

et al.

Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. Arthritis Rheum 2004; 50: 2048–2065.

25.

Liu

Manzi

Ahearn

. Biomarkers for systemic lupus erythematosus: a review and perspective. Curr Opin Rheumatol 2005; 17: 543–549.

26.

Chen

Zhang

et al.

MicroRNA-346 mediates tumor necrosis factor alpha-induced downregulation of gut epithelial vitamin D receptor in inflammatory bowel diseases. Inflamm Bowel Dis 2014; 20: 1910–1918.

27.

Huang

Zhang

et al.

Vitamin D receptor down-regulation is associated with severity of albuminuria in type 2 diabetes patients. J Clin Endocrinol Metab 2016; 101: 4395–4404.