Fig. 4

MiR-181a-5p-enriched MSC-EVs inhibit the expression of GRP78. A. Schematic illustration of filtrating potential GRP78-targeting miRNAs from TargetScan, miRanda, and miRDB. B. Heat map of miRNAs profiles in MSCs and MRC5. C. Relative miRNA levels in MSCs (n = 5). ^****P < 0.0001 vs miR-181b-5p, miR-181c-5p, and miR 181d-5p. D. Heat map of miRNA profiles in MSC-EVs and MRC5-EVs. E. Relative expression of miRNAs in MSC-EVs (n = 5). ^***P < 0.001, ^****P < 0.0001 vs miR-181b-5p, miR-181c-5p, and miR 181d-5p. F. Schematic design of the GRP78 labeled double-luciferase reporter system. G. The inhibiting efficacy of miR-181a-5p on GRP78 (n = 5). ^****P < 0.0001 vs miR-181a-5p (0 μmol/L). ^####P < 0.0001 vs miR-181a-5p (50 μmol/L). H. The intensifying efficacy of anti-miR-181a-5p in GRP78 (n = 5). ^***P < 0.001, ^****P < 0.0001 vs anti-miR-181a-5p (0 μmol/L). ^####P < 0.0001 vs anti-miR-181a-5p (50 μmol/L). I and J. Western Blotting and quantitative GRP78 expression in cardiomyocytes exposed to PBS (Control), Dox/PBS, Dox/Mimic^NC, and Dox/Mimic^{miR−181a−5p}, (n = 3). ^****P < 0.0001 vs Control, ^####P < 0.0001 vs Dox/PBS. ^&&&&P < 0.0001 vs Dox/Mimic.^NC. Data were analyzed by one-way ANOVA followed by Bonferroni post hoc test, unless specifically indicated