AB0197 VITAMIN D PROTECTS PODOCYTES FROM AUTOANTIBODIES INDUCED INJURY IN LUPUS NEPHRITIS BY REDUCING ABERRANT AUTOPHAGY
Authors: Qi Yu, Zhaohui Zheng, Zhangsuo Liu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Recent data suggest that vitamin D insufficiency may play a role in the progression of SLE and the nephropathy such as chronic kidney disease[1]. We previously show that severe vitamin D deficiency increases the risk for moderate to severe disease activity[2]. Moreover, vitamin D has been demonstrated a protective effect on podocyte injury via diverse mechanisms in proteinuric glomerular disease[3-7]. However, there is a paucity of data to demonstrated the mechanisms through which the autophagy functions on the protective role vitamin D plays on podocyte in the pathogenesis of lupus nephritis <h3>Objectives</h3> The aim of this study was to investigate whether vitamin D play a protective role in podocyte injury induced by autoantibodies purified from lupus nephritis (LN) patients serum via autophagic way. <h3>Methods</h3> Autophagic activities of LN patients renal tissues were evaluated under transmission electronic microscope. IgG from patients with LN were purified to induce human podocyte injury and the role of vitamin D in injury was observed. Podocytes were observed under TEM and autophagic activity was evaluated by western blot analysis and qRT-PCR, mRFP-GFP-LC3B adenovirus were infected into HPC in vitro. <h3>Results</h3> Significantly higher autophagic levels were observed in LN patients<i>(p</i>&lt;0.05) and apparently greater autophagic levels in podocytes were shown (<i>p</i>&lt;0.05). Among different classifications of LN, Class V(n=5), III+V(n=5) and IV+V (n=5) gained higher autophagic levels than Class III(n=5) and IV(n=5). Induced autophagy, which was evident by increased LC3B-II and Beclin 1 level, caused consumption of p62, more autophagosomes observed under TEM, and more LC3B dots observed under confocal microscope in IgG group, along with decreased Nephrin expression, which suggests podocyte injury. Reduction of autophagy as well as alleviated podocyte injury was observed in the IgG+ VD group. <h3>Conclusion</h3> This study demonstrates that vitamin D plays a protective role in podocytes injury induced by autoantibodies from LN patients and that appears to be a novel therapy target in LN. <h3>References</h3> [1] Mok CC, Bro ET, Ho LY, Singh RJ, Jannetto PJ: Serum 25-hydroxyvitamin D3 levels and flares of systemic lupus erythematosus: a longitudinal cohort analysis. Clinical rheumatology 2018. [2] Gao CC, Liu SY, Wu ZZ, Li TF, Gao GM, Liu ZS, Zheng ZH: Severe vitamin D deficiency increases the risk for moderate to severe disease activity in Chinese patients with SLE. Lupus 2016, 25(11):1224-1229. [3] Vitamin D down-regulates TRPC6 expression in podocyte injury and proteinuric glomerular disease. The American journal of pathology 2013, 182(4):1196-1204. [4] Zhang XL, Guo YF, Song ZX, Zhou M: Vitamin D prevents podocyte injury via regulation of macrophage M1/M2 phenotype in diabetic nephropathy rats. Endocrinology 2014, 155(12):4939-4950. [5] Guo J, Lu C, Zhang F, Yu H, Zhou M, He M, Wang C, Zhao Z, Liu Z: VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2017, 43(1):39-51. [6] Chandel N, Ayasolla K, Wen H, Lan X, Haque S, Saleem MA, Malhotra A, Singhal PC: Vitamin D receptor deficit induces activation of renin angiotensin system via SIRT1 modulation in podocytes. Experimental and molecular pathology 2017, 102(1):97-105. [7] Garsen M, Sonneveld R, Rops AL, Huntink S, van Kuppevelt TH, Rabelink TJ, Hoenderop JG, Berden JH, Nijenhuis T, van der Vlag J: Vitamin D attenuates proteinuria by inhibition of heparanase expression in the podocyte. The Journal of pathology 2015, 237(4):472-481. <h3>Disclosure of Interests</h3> None declared