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Type of publication: Journal Article
Type of document: Full Paper

Year: 2020

Authors: Bukosza, EN; Kornauth, C; Hummel, K; Schachner, H; Huttary, N; Krieger, S; Nöbauer, K; Oszwald, A; Razzazi Fazeli, E; Kratochwill, K; Aufricht, C; Szénási, G; Hamar, P; Gebeshuber, CA

Title: ECM Characterization Reveals a Massive Activation of Acute Phase Response during FSGS.

Source: Int J Mol Sci. 2020; 21(6):2095


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VetCore (Proteomics);

Authors Vetmeduni Vienna:

Hummel Karin
Nöbauer Katharina
Razzazi-Fazeli Ebrahim

Vetmed Research Units
VetCore


Abstract:
The glomerular basement membrane (GBM) and extra-cellular matrix (ECM) are essential to maintain a functional interaction between the glomerular podocytes and the fenestrated endothelial cells in the formation of the slit diaphragm for the filtration of blood. Dysregulation of ECM homeostasis can cause Focal segmental glomerulosclerosis (FSGS). Despite this central role, alterations in ECM composition during FSGS have not been analyzed in detail yet. Here, we characterized the ECM proteome changes in miR-193a-overexpressing mice, which suffer from FSGS due to suppression of Wilms' tumor 1 (WT1). By mass spectrometry we identified a massive activation of the acute phase response, especially the complement and fibrinogen pathways. Several protease inhibitors (ITIH1, SERPINA1, SERPINA3) were also strongly increased. Complementary analysis of RNA expression data from both miR-193a mice and human FSGS patients identified additional candidate genes also mainly involved in the acute phase response. In total, we identified more than 60 dysregulated, ECM-associated genes with potential relevance for FSGS progression. Our comprehensive analysis of a murine FSGS model and translational comparison with human data offers novel targets for FSGS therapy.


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