The following is the summary of “Comparative proteomic analysis of children FSGS FFPE tissues,” published in the December 2022 issue of Pediatrics by Ni, et al.
In children, steroid-resistant nephrotic syndrome (SRNS) is typically caused by focal segmental glomerulosclerosis (FSGS). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), researchers analyzed the protein profiles of renal tissue that had been formalin-fixed and paraffin-embedded (FFPE) to determine potential candidates and the mechanism of steroid resistance. In addition, 7 children with steroid-sensitive (SS) FSGS and 11 with steroid-resistant (SR) FSGS had renal biopsies taken. Investigators used a liquid chromatography-tandem mass spectrometer (LC-MS/MS) to analyze protein patterns in formalin-fixed paraffin-embedded (FFPE) kidney tissue.
Protein-protein interaction (PPI) network building, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were also carried out. Immunohistochemistry staining confirmed the presence of two proteins in FSGS patients and mouse models. Study group quantified more than 4,000 proteins altogether, and of those, 325 were identified as differentially expressed proteins (DEPs) between the SS and SR groups (foldchange ≥2, P<0.05). According to the GO analysis, the most significantly up-regulated proteins were mostly involved in protein transportation, regulation of the complement activation process, and cytolysis.
Differential pathways (lysosome, terminal pathway of complement) were also observed between the 2 categories by cluster analysis. LAMP1 and ACSL4 were chosen as 2 of these possible candidates to undergo validation analyses. It was shown that LAMP1 was more highly expressed in the glomerulus, while ACSL4 was more highly expressed in the tubular epithelial cells. This investigation sought to determine the causes and contributors to steroid resistance in pediatric FSGS patients. These proteome alterations in children with FSGS may prove useful for identifying treatment targets and predicting outcomes.
Source: bmcpediatr.biomedcentral.com/articles/10.1186/s12887-022-03764-7