Fig. 6.

Au₃-PEG₅₀₀-FA₃₂ NP inhibited ECM-related genes and p-p38α in the UUO kidney. (A) UUO mice were treated with a single i.v. dose of Au₃-PEG₅₀₀-FA₃₂ NP, saline, or free FA on day 7 post-UUO surgery and then killed on day 9. (B) Venn diagram of differentially expressed genes (DEGs) identified in pairwise comparisons between the three treatment groups (Q < 0.05). Numbers in the overlapping region between two or more circles indicate the number of DEGs shared between the pairwise comparisons. Note that “Group X vs. Group Y” shows statistically significant changes in RNA expression that were found in Group X with reference to Group Y as baseline. There are 169 common DEGs in the “Au₃-PEG₅₀₀-FA₃₂ NP vs. saline” and “Au₃-PEG₅₀₀-FA₃₂ NP vs. free FA” pairwise comparisons (red border in Venn diagram). (C) Of the 169 common DEGs, 18 of them have FPKM values > 2 for the UUO kidneys analyzed by RNA-seq. (D) The heatmap shows that Au₃-PEG₅₀₀-FA₃₂ NP treatment down-regulated genes related to collagen and up-regulated genes related to vesicle transport when compared to free FA and saline treatments. (E and F) Percent inhibition of p38α and MAPKAPK2 by Au₃-PEG₅₀₀-FA₃₂ (black) and Au₃-PEG₅₀₀ NP (red) using the Z-Lyte assay. (G) IC₅₀ values of Au₃-PEG₅₀₀-FA₃₂ and Au₃-PEG₅₀₀-FA₃₂ NPs. (H) Western blot analysis revealed significant inhibition of p-p38α upon treatment with Au₃-PEG₅₀₀-FA₃₂ NP when compared to saline. Data are from n = 3, across one experiment. (I) ELISA analysis of the UUO kidney revealed significant inhibition of p-p38α upon treatment with Au₃-PEG₅₀₀-FA₃₂ NP when compared to saline. Data are from n = 3, across one experiment. In (H) and (I), statistical significance was evaluated using the Mann–Whitney U test. All P values ≤ 0.05 are displayed on the graphs. All bars and error bars represent mean ± SD.