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Abstract: TH-PO0421

Quantitative Serum Ubiquitylome Profiling Identifies Novel Apolipoprotein Biomarkers in Idiopathic Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Xiao, Yichen, Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong, China
  • Ma, Hualin, Shenzhen People's Hospital Department of Nephrology, Shenzhen, Guangdong, China
Background

Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in which lipid metabolism disorders play a key role. While ubiquitination regulates lipid metabolism, its landscape in IMN remains unexplored. We characterized the IMN serum ubiquitylome to elucidate pathogenesis and identify biomarkers.

Methods

Serum samples were collected from 12 untreated IMN patients and 10 healthy controls (HCs). A quantitative proteomics approach was used to identify differentially expressed ubiquitination sites and their corresponding proteins on a large scale. Differentially ubiquitinated sites and proteins were evaluated by GO, KEGG, and PPI network analysis.

Results

IMN patients exhibited 12 significantly downregulated ubiquitination sites across 10 proteins compared to HCs. Bioinformatics analyses revealed that these proteins were significantly enriched in cholesterol metabolism, the PPAR signaling pathway, and lipid transport. Moreover, PPI network analysis identified UBC, APOC3, APOA2, and APOD as hub proteins.

Conclusion

Downregulation of ubiquitination levels in specific apolipoproteins may contribute to IMN pathophysiology by disrupting the lipid metabolism network. This study offers a novel omics perspective on IMN pathogenesis and identifies potential biomarkers for early diagnosis and targeted intervention.

Volcano plot and heat map of differentially expressed ubiquitination sites.

GO and KEGG pathway based on the differentially ubiquitinated proteins.

Funding

  • Government Support – Non-U.S.