Fig. 7: Exercise with AICAR treatment resulted in a pro-inflammatory and pro-apoptotic FAP phenotype that promotes muscle regeneration.
a–c Representative images of PDGFRα- and p16INK4A-immunostained triceps surae (green and red, respectively) (a), and quantitative data of the number of FAPs (b) and the percentage of p16INK4A+ FAPs (c) in randomly chosen fields of view (n = 3 for control, n = 4 for exercise and CIM). d Representative confocal images of Bcl-2-, p53-, IL-33-, and p16INK4A-immunostained FAPs isolated from CIM with or without AICAR treatment in vitro. e Hierarchical clustering of differentially expressed cytokine–cytokine receptor gene expression was profiled by PrimerArray® analysis in control, AMI, and CIM mice (the average value is that shown in Fig. 2d; n = 3 per group), and control exercise, CIM exercise, CIM AICAR, and CIM exercise with AICAR (n = 3 per group). Genes with higher expression are depicted in magenta, genes with lower expression are depicted in cyan, and genes with no difference are depicted in black. f Principal component analysis (PCA) of FAPs isolated from control, control exercise, CIM, CIM exercise, CIM AICAR, and CIM exercise with AICAR. g Proposed mechanism whereby exercise-induced FAP senescence promotes muscle regeneration. Data are shown as a dot plot for each specimen, and as means as well as medians with IQRs and 1.5 times the IQR by dot plots and box and whisker plots. P values were determined by the one-way ANOVA adjusted by the Holm method (*P < 0.05, **P < 0.001).
