Fig. 7
RGLS4326 improves expression of dysregulated gene networks in PKD models. a Schematic illustration of RGLS4326-mediated inhibition of miR-17. RGLS4326 displaces miR-17 from the translationally active polysome fractions and de-represses miR-17 target genes including Pkd1 and Pkd2 and their encoded proteins PC1 and PC2. b–e RNA-seq analysis was performed to compare mRNA expression profiles between kidneys from non-transgenic (n = 12), PBS-treated Pkd2-KO (n = 8), RGLS4326-treated Pkd2-KO (n = 11), and control oligo-treated Pkd2-KO mice (n = 8). RNA-seq analysis was also performed from wild-type (n = 2), PBS-treated Pcy/CD1 (n = 4), RGLS4326-treated Pcy/CD1 (n = 4), and control oligo-treated Pcy/CD1 mice (n = 3). b–c Kolmogorov-Smironov test statistics comparing the cumulative distribution of global mRNA changes between RGLS4326-treated vs. PBS-treated kidney samples indicated significant de-repression of predicted miR-17 target genes (as defined by TargetScanMouse v7.1) after RGLS4326 treatment in Pkd2-KO (green triangle) and Pcy/CD1 model (inverted green triangle). d–e Comparative differential expression analysis demonstrated a clear trend in global transcriptomic changes where dysregulated gene expression in Pkd2-KO (blue circles) and Pcy/CD1 kidneys (black circles) (x-axis) were improved after RGLS4326 treatment (y-axis). Rho-values and slopes from corresponding Spearman’s correlations are shown. RGLS4326 treatment improves the expression of 994 genes in Pkd2-KO (n = 11) and 658 genes in Pcy/CD1 kidney (n = 4) (FDR < 0.05 and Log2FC > ∣0.5∣). f Top 15 pathways as predicted by the ingenuity pathway analysis software (based on ∣z-scores∣) potentially responsible for the gene changes are shown. Positive z-scores (shades of orange) indicate activation, while negative z-scores (shades of blue) indicate repression. Source data for Fig. 7f is provided in Source data files
