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

Abstract

SubjectThe 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.MethodsAutophagic 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.ResultsSignificantly 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.ConclusionThis 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.

Morroniside Inhibits H2O2-Induced Podocyte Apoptosis by Down-Regulating NOX4 Expression Controlled by Autophagy In Vitro

“…For example, in patients with diabetes (Wu et al, 2018;Zhao et al, 2018;Li et al, 2020) and IgA nephropathy (Liang et al, 2018), decreased podocyte autophagy activity is observed; while in systemic lupus erythematosus (SLE) (Jin et al, 2018) or adriamycin-induced models of nephrotic syndrome (Yu et al, 2018), podocyte autophagy activity is found to be increased. Yu et al (2019) observed an increase in the number of autophagosomes and the expression of autophagy-related proteins such as LC3B-II and Beclin-1 in podocytes stimulated by lupus autoantibodies. In the present study, the expression of LC3-II and the number of autophagosomes decreased after H 2 O 2 treatment, suggesting that the formation of autophagosomes was blocked.…”

Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome

“…Thus, we evaluated the number of autophagic vacuoles alone. The appearance of autophagy should be further investigated in other forms of human glomerular diseases, including lupus nephritis [45] and diabetic nephropathy [26]. The mechanism of interaction between autophagy and FPE in podocytes is largely unknown.…”

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

“…Considering the role of vitamin D deficiency on the development of SLE, Yu et al ( 141 ) recently demonstrated that vitamin D plays a protective role in the autoantibody-induced injury of podocytes (kidney cells that wrap around capillaries of the glomerulus) in patients with lupus nephritis, which could be a potential novel therapeutic target to treat lupus nephritis. From a 24 week double-blind randomized placebo-controlled trial by Lima et al ( 142 ), it was established that supplementation of vitamin D in patients with juvenile-onset SLE effectively improved parameters of bone microarchitecture ( p = 0.024).…”