Dataset Information

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

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.

SUBMITTER: Bukosza EN

PROVIDER: S-EPMC7139641 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Bukosza Eva Nora EN Kornauth Christoph C Hummel Karin K Schachner Helga H Huttary Nicole N Krieger Sigurd S Nöbauer Katharina K Oszwald André A Razzazi Fazeli Ebrahim E Kratochwill Klaus K Aufricht Christoph C Szénási Gabor G Hamar Peter P Gebeshuber Christoph A CA

International journal of molecular sciences 20200318 6

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 chang ...[more]

PMID: 32197499

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

Publications

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

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