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. 2019 Sep 19;4(18):e99271. doi: 10.1172/jci.insight.99271

Figure 1. mTOR-mediated podocyte hypertrophy as a compensatory response to human somatic growth and FSGS.

Figure 1

(A) Transcriptional regulation of mTOR signaling in glomerular extracts from human biopsies. Comparison between FSGS (n = 23) and living donors (n = 42), showing fold-change of each respective gene (q < 0.05 in all genes except those with NS), and representative confocal image from indirect immunofluorescence showing a podocyte specific marker (Wilms’ Tumor 1; WT-1) and a downstream target of mTORC1 (phosphorylated ribosomal protein S6; p-rp-S6) in a glomerulus from a patient with primary FSGS. Scale bar: 10 μm. (B) Transcriptional regulation of PEC activation–related genes in glomerular extracts from human biopsies. Comparison between FSGS (n = 23) and living donors (n = 42), showing fold-change of each respective gene (q < 0.05 in all genes except those with no significance [NS]) and representative confocal image of PEC activation marker CD44, and histological staining (periodic acid–Schiff; PAS) showing sequential physical sections of a glomerulus with a segmental lesion (arrowhead). Scale bars: 100 μm. (C) Correlation analysis of regulated mTOR signaling and PEC activation genes. Each box represents an independent association (spearman rank coefficient; R). Every association was statistically significant unless labeled with NS. (D) Comparison of podocyte depletion indices (podocyte number, PN; podocyte density, PD) between glomeruli from children, adults, and adults with FSGS. (E) Association between podocyte number and glomerular volume (using Spearman’s rank coefficients) among children (blue), adults (gray), and adults with FSGS (red). Solid lines represent the regression line, and dotted lines the 95% CI. (F) Comparison of podocyte size indices (total podocyte volume divided by podocyte number, TPV:PN ratio; and total podocyte volume divided by podocyte density, TPV:PD ratio) between children, adults, and adults with FSGS. ****P < 0.0001; ***P < 0.001. In violin plots, red lines represent medians and blue lines represent IQRs; every gray dot represents 1 glomerulus. Kruskal-Wallis with Dunn’s multiple comparisons tests were used.