Abstract: TH-PO817
The Differences in Podocyte Injury Between IgA Nephropathy and Membranous Nephropathy Based on Proteomics Analysis
Session Information
- Glomerular Diseases: Immunology and Inflammation - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Chen, Xizhao, Chinese PLA General Hospital, Beijing, BeiJIng, China
- Wu, Di, General hospital of PLA, Beijing, China
- Cai, Guangyan, Chinese PLA General Hospital, Beijing, BeiJIng, China
- Chen, Xiangmei, Chinese PLA General Hospital, Beijing, BeiJIng, China
Background
IgA nephropathy (IgAN) is the most common primary glomerular nephritis worldwide. Currently, the diagnosis has to depend on renal biopsy which is an invasive practice. The developing proteomics can provide new ideas for exploring the potential biomarkers and pathogenesis of IgAN.
Methods
The renal tissue of 59 patients with IgAN was obtained and screened for differential protein expression (DEPs) profile by a high throughput method liquid chromatography-mass (LC-MS). The results in IgAN were compared to those in 9 patients with membranous nephropathy (MN) and 19 cases of adjacent normal tissues from renal cell carcinoma. Specific proteins in IgAN and MN were selected. Histochemical stain and double-labelling immunofluorescence stain were used to locate the proteins expressed in IgAN and MN. siRNA and stimulus were used to establish the gene expression cell models, and genes and proteins were detected by RT-PCR and western blot.
Results
(1) An overall sum of 6636 proteins were identified in IgAN, MN and normal tissue. There were 1086 DEPs in IgAN and 392 specific DEPs in IgAN when compared with MN. (2) Samples from patients with IgAN and MN were clearly distinguishable from normal controls. (3) Specific podocyte marker proteins such as nephrin and podocin were down-regulated both in IgAN and MN. Specific DEP CD151, which is a membrane protein of podocyte, was down-regulated in IgAN and has no expression change in MN. Histochemical stain and double-labing IF stain showed CD151 was located in IgAN and its expression was lower and weaker than that in MN and normal tissue. Specific DEP PLA2R1, which is a specific podocyte membrane protein, was significantly up-regulated in MN and has no expression change in IgAN. Histochemical stain showed PLA2R1 was higher and stronger expressed in the podocyte of MN. (4) TNFα could suppress CD151 expression and VEGFA could upregulate PLA2R1 expression in human primary podocyte, and down regulation of VEGFA in podocyte by siRNA could suppress the expression of PLA2R1.
Conclusion
Our study identified the differential expression of proteins in IgAN and MN tissues based on the proteomics analysis and detected the specific proteins CD151 and PLA2R1. TNFα-induced CD151 down-expression and VEGFA-induced PLA2R1 activation in podocyte might be one of the mechanisms in IgAN and MN that cause podocyte injury.