Fig. 6
Significant differences in the miRNA expression profile between MSCs-exo and MSCsTXL-exo. A Heatmap of upregulated and downregulated miRNAs in MSCsTXL-exo compared to MSCs-exo (n = 3). B Volcano plot showing the significantly differentially expressed miRNAs (twofold change and p < 0.05 as the threshold) in MSCsTXL-exo compared to MSCs-exo. C The overlap of upregulated miRNAs in MSCsTXL-exo according to miRNA sequencing analysis and the main reported miRNAs participating in inflammation modulation and cardiac repair. miR-146a-5p stood out as the candidate effector. qRT-PCR validation of miR-146a-5p levels in exosomes (D) (n = 4) and MSCs (E) (n = 4). F miR-146a-5p levels in the infarct border zone of PBS, MSCs-exo or MSCsTXL-exo-treated rat hearts (n = 6). G miR-146a-5p levels in H9C2 cells that were cocultured with PBS, MSCs-exo or MSCsTXL-exo for 24 h (n = 4). miR-146a-5p levels in MSCsTXL (H) or exosomes (I) derived from MSCsTXL treated with miR-146a-5p inhibitors or its negative control (NC) (n = 4). J Representative images of the flow cytometry assay and quantification (K) of apoptosis after treatment with MSCsTXL-inhibitors-exo or MSCsTXL-inhibitors-NC-exo (n = 5). Western blotting images (L) and quantification of Bax (M) and cleaved-Caspase 3 (N) levels in H9C2 cells after treatment with MSCsTXL-inhibitors-exo or MSCsTXL-inhibitors-NC-exo (n = 4). All data are expressed as the mean ± SD and were analyzed with Student’s t test or one-way ANOVA. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001