Vitamin D protects podocytes from autoantibodies induced injury in lupus nephritis by reducing aberrant autophagy

• Published in: Arthritis research & therapy Vol. 21; no. 1; p. 19
• Main Authors: Yu, Qi, Qiao, Yingjin, Liu, Dongwei, Liu, Fengxun, Gao, Congcong, Duan, Jiayu, Liang, Lulu, Di, Xueqi, Yuan, Yi, Gao, Yukui, Cui, Siwan, Qin, Yilu, Li, Tianfang, Zheng, Zhaohui, Liu, Zhangsuo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.01.2019; BioMed Central; BMC
• Subjects: Adenoviruses; Adolescent; Adult; Antibodies; Arthritis; Autoantibodies; Autoantibodies - blood; Autoantibodies - drug effects; Autoimmune diseases; Autoimmunity; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Autophagy - physiology; Care and treatment; Cell Line, Transformed; Child; Disease; Female; Hepatitis; Homeostasis; Humans; Immunoglobulin G; Immunoglobulins; Kidney diseases; Kidneys; Kinases; Lupus; Lupus nephritis; Lupus Nephritis - blood; Lupus Nephritis - drug therapy; Lupus Nephritis - pathology; Male; Middle Aged; Nephritis; Nephrology; Novels; Pathogenesis; Podocyte; Podocytes - drug effects; Podocytes - metabolism; Podocytes - ultrastructure; Polymerase chain reaction; Vitamin D; Vitamin D - pharmacology; Vitamin deficiency; Vitamins; Young Adult; Podocyte; Lupus nephritis; Vitamin D; Autophagy
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-018-1803-9

The aim of this study was to investigate whether vitamin D plays a protective role in podocyte injury induced by autoantibodies purified from the serum of patients with lupus nephritis (LN) via reducing aberrant autophagy. Autophagic activities of renal tissues of patients with LN were evaluated under transmission electronic microscope (TEM). Immunoglobulin G (IgG) from patients with LN was purified to induce human podocyte injury, and the role of vitamin D in injury was observed. Podocytes were observed under TEM, autophagic activity was evaluated by western blot analysis and quantitative real-time polymerase chain reaction, and mRFP-GFP-LC3B adenovirus was infected into human podocytes in vitro. Significantly higher autophagic levels were observed in patients with LN (P <0.05), and apparently greater autophagic levels in podocytes were shown (P <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 the 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+ vitamin D group. This study demonstrates that vitamin D plays a protective role in podocyte injury induced by autoantibodies from patients with LN and appears to be a novel therapy target in LN.