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Abstract: TH-PO774

Podocyte Infolding Glomerulopathy: Insights from Proteomics by Laser Microdissection and Mass Spectrometry

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Hong, Ling, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
  • Zheng, Zhihua, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
  • Chen, Wenfang, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Background

Podocyte infolding glomerulopathy (PIG) is a newly recognized rare glomerular injury. The potential mechanism of this injury pattern remains unclear.

Methods

10 cases diagnosed with PIG and 5 minimal change disease (MCD), 4 donor kidney biopsy specimens at Kingmed Diagnostics were analyzed by laser scanning microdissection and mass spectrometry (LMD/MS). The clinicopathological features, especially the ultrastructural changes were reviewed.

Results

10 cases were divided into 2 groups according to immunofluorescence, IC-PIG (coexisting with immune-complex associated glomerulonephritis), and isolate PIG (without immunoglobulin or complement deposition). The underlying disease of IC-PIG included lupus nephritis in 4 cases, and membranous nephropathy in 1 case, while no known underlying disease was found in 5 cases of isolate PIG. Immunoglobulin gamma-1 heavy chain (IGG1) and Immunoglobulin heavy constant gamma 3 (IGHG3) showed significant differences in the IC-PIG group compared with the other two control groups. The differentially expressed protein, α-actinin4 (ACTN4), was detected by LMD/MS in 10 PIG glomeruli (P=0.005) compared with 9 controls, among the top 20 proteins. The displacement of ACTN4 into the GBM was confirmed by the confocal microscope. Interestingly, Tubulin Beta-4 Chain (TUBB4A) was only detected in the isolate group compared with IC-PIG, normal donor kidney and MCD among the identified 302 proteins. Regulation of actin cytoskeleton signaling was screened out by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.

Conclusion

PIG is a rare morphological change of podocyte injury with heterogeneous diseases. Podocyte cytoskeletal protein ACTN4 and TUBB4A were dysregulated which may involve in the mechanism of podocyte injury.

Mass spectrometry and confocal imaging.