Differential Effects of Circulating IgA Isolated from Patients with IgA Nephropathy on Superoxide and Fibronectin Production of Mesangial Cells

Abstract

Background: IgA nephropathy (IgAN) is characterized by predominant deposition of IgA in the glomerular mesangium. Serum IgA is often elevated in patients with IgAN, and it has been postulated that it is responsible for the mesangial lesions. However, the direct effect of circulating IgA on mesangial cells is not clear. Methods: We investigated the effects of sera and IgA which were isolated from patients with IgAN on thymidine uptake, superoxide and fibronectin production and fibronectin mRNA expression of cultured rat mesangial cells, and we compared the findings to the effects of IgA isolated from patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN) and normal controls. IgA was isolated with affinity chromatography using cyanogen bromide activated Sepharose 4B coupled to sheep antihuman IgA antiserum. Results: Our results demonstrated that both sera and IgA from patients with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by ³H-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than that of sera and IgA isolated from patients with MsPGN and normal controls. Sera and IgA from patients with IgAN significantly enhanced superoxide and fibronectin production and fibronectin mRNA expression of mesangial cells. The superoxide and fibronectin production was also significantly higher as compared with patients with MsPGN and normal controls. Conclusions: Our results indicate that circulating IgA isolated from patients with IgAN is different from that of patients with MsPGN and normal controls and may potentially induce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN.

Exploration of Artemisinin Against IgA Nephropathy via AKT/Nrf2 Pathway by Bioinformatics and Experimental Validation

“…Among this two, response to reactive oxygen species (ROS) attracted our attention. Studies have shown that high levels of oxidative stress exist in both plasma 19 , 20 and renal tissue especially mesangial cells 21 , 22 of IgAN patients. Our GSEA analysis suggested a decreased reflection to oxidative stress and antioxidant capacity in the transcriptome of patients.…”

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“…The tracer used was alkaline phosphatase‐labelled human fibronectin. Samples were analysed with a spectrophotometer at 403 nm 10 …”

Oxidative Stress in IgA Nephropathy

“…The activation of intracellular signaling mostly results in oxidative stress, as detected in mesangial cells cultured with aberrantly glycosylated IgA or IgA aggregates [7,8] and in renal biopsies of patients with IgAN, similar to what has been detected in diabetic nephropathy [9]. Signs of altered oxidation/antioxidation balance have been detected in sera and/or in erythrocytes of patients with IgAN, including increased levels of lipoperoxide or malondialdehyde and reduced activity of superoxide dismutase, catalase and glutathione peroxidase [10,11].…”