Fig. 4: Uridine enhances muscle regeneration in vivo.

a Schematic diagram showing the summarized phenotypes in tissue regeneration or repair models. b Schematic diagram for the time course of the mouse muscle cryoinjury and vehicle or uridine treatment. c Left, haematoxylin and eosin (H&E) staining of the skeletal muscle derived from sham mice (n = 10 mice) and mice treated with vehicle (n = 10 mice) or uridine (n = 10 mice) post cryoinjury. Right, quantitative data of mean myofiber cross-sectional area (CSA) in the skeletal muscle derived from sham mice and mice treated with vehicle or uridine post cryoinjury. Data are presented as the means ± SEM (two-tailed unpaired Student’s t-test). Scale bars, 100 μm. d Left, Masson staining of the quadriceps femoris derived from sham mice (n = 9 mice) and injured mice treated with vehicle (n = 9 mice) or uridine (n = 9 mice). Right, quantitative data of the fibrotic area. Data are presented as the means ± SEM (two-tailed unpaired Student’s t-test). Scale bars, 100 μm. e ELISA detecting the secretion of proinflammatory factors in the serum of sham mice (n = 20 mice) and mice treated with vehicle (n = 25 mice) or uridine (n = 25 mice) post cryoinjury. Data are presented as means ± SEM (two-tailed unpaired Student’s t-test). f Grip strength evaluation of the hind limbs of sham mice (n = 15 mice) and mice treated with vehicle (n = 15 mice) or uridine (n = 15 mice) at day 7 post cryoinjury. Data are presented as means ± SEM (two-tailed unpaired Student’s t test). g Treadmill distance of sham mice (n = 15 mice) and mice treated with vehicle (n = 15 mice) or uridine (n = 15 mice) at day 7 post cryoinjury. Data are presented as means ± SEM (two-tailed unpaired Student’s t-test). h Gene set enrichment analysis showing relative expression levels for downregulated DEGs upon cryoinjury (top) and upregulated DEGs upon cryoinjury (bottom) in the muscle tissues derived from vehicle- or uridine-treated mice. i Top, Venn diagram showing the downregulated genes upon cryoinjury and upregulated genes upon uridine treatment as compared to vehicle treatment. The overlapped genes were defined as “rescue DEGs (upregulated)” (left). Ring-heatmap plot showing the relative expression levels of “rescue DEGs (upregulated)” in mouse muscle regeneration model (right). Bottom, Venn diagram showing the upregulated genes upon cryoinjury and downregulated genes upon uridine treatment as compared to vehicle treatment. The overlapped genes were defined as “rescue DEGs (downregulated)” (left). Ring-heatmap plot showing the relative expression levels of “rescue DEGs (downregulated)” in mouse muscle regeneration model (right). The color key from blue to amaranth indicates log₂(fold change) values from low to high. j Top, GO term and pathway enrichment analysis of “rescue DEGs (upregulated)” in mouse muscle regeneration model. Bottom, GO term and pathway enrichment analysis of “rescue DEGs (downregulated)” in mouse muscle regeneration model. The color keys from white to red or blue indicate –log₁₀(P-value) from low to high.