MOLECULAR ALTERATIONS OF PODOCYTES IN PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND IMMUNOGLOBULIN A NEPHROPATHY: AN EXPLORATORY STUDY

Introduction:

This study explored on the premise that the molecular phenotype of podocytes can be altered in immune glomerulopathies, with particular emphasis on the expression of molecules of epithelial and mesenchymal phenotypes.

Methods:

The study included 14 cases of primary FSGS (pFSGS), 12 cases of IgA nephropathy (IgAN) and 12 negative controls (NC). NC was represented by samples of unaltered renal cortex of non-proteinuric patients undergone laparoscopic nephrectomy. In all cases, we performed quantitative immunomorphological studies of Wilms’ tumour protein (WT1), podocin (Nphs2) and podocyte mesenchymal markers (desmin, vimentin, nestin) to evaluate their expression in glomeruli. Clinical data on estimated glomerular filtration rate (eGFR), serum albumin and daily proteinuria

Results:

Primary FSGS cases had nephrotic syndrome and typical glomerular alterations by light microscopy and ultrastructural analysis. In IgAN, proteinuria was less severe (Fig 1). eGFR levels in pFSGS and IgAN were similar (Fig 1).

Compared to IgAN and NC groups, pFSGS showed a lower glomerular WT1 expression, Nphs2 Fig 1, 2) but higher expression of intermediate cytoskeleton filaments (IF), desmin, and nestin (Fig 1, 3). In both pFSGS and IgAN, there was a reduction in glomerular Nphs2 expression vs. NC (Fig 1, 2).

WT1 and Nphs2 were closely correlated (r=0.51, p<0.05), and both were negatively associated with proteinuria (-0.45 and -0.50, respectively; p<0.05).

In pFSGS, WT1 was negatively correlated with desmin (-0.74, p<0.05) that predominantly localised in WT1-negative glomerular areas by confocal microscopy (Figure 4). Decreased WT1 and increased desmin in the parietal epithelium were also found to characterise pFSGS (Fig. 1).

Conclusions:

Bidirectional alterations in the glomerular expression of podocyte markers (WT1, Nphs2) and intermediate filament proteins are apparent in pFSGS. These findings could suggest for the epithelial-mesenchymal transition of podocytes and the parietal epithelium, determining the structural and functional disorders of these cells.

I have potential conflict of interest to disclose.
The research was funded by the Russian Science Foundation (project No. 23-15-00510)

I did not use generative AI and AI-assisted technologies in the writing process.