ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO817

The Differences in Podocyte Injury Between IgA Nephropathy and Membranous Nephropathy Based on Proteomics Analysis

Session Information

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.