Fig. 4

Inhibition of miR-222 prevents exercise-induced cardiomyogenesis. a miR-222 is upregulated after eight weeks of voluntary wheel running in young adult mice (n = 6 mice per group, *p = 0.01, Student’s t test). b Mice underwent simultaneous ¹⁵N-thymidine infusion and LNA-anti-miR-222 or control LNA-anti-miR (LNA-Ctr) treatment for 8 weeks of sedentary activity or voluntary wheel running. miR-222 inhibition blocks physiologic cardiac hypertrophy measured by heart weight/tibia length (HW/TL) (n = 5 mice per group, *p < 0.05 running LNA-anti-miR-222 vs. running LNA-Ctr, ^#p < 0.05 running LNA-Ctr vs. sedentary LNA-anti-miR-222, one-way ANOVA with Tukey’s post-test for multiple comparisons). c Similar to exercise only, exercised mice injected with LNA-Ctr for 8 weeks show an increase in ¹⁵N-thymidine-positive cardiomyocytes. However, exercised mice treated with LNA-anti-miR-222 demonstrate a reduced number of ¹⁵N-thymidine-positive cardiomyocytes closer to sedentary baseline levels (800–1350 cells from four mice per group were counted *p = 0.0255, Fisher’s exact test). d Contingency table showing the absolute numbers and percentage calculations of ¹⁵N-positive and ¹⁵N-negative cardiomyocytes. e Exercised mouse hearts show downregulation of miR-222 target HIPK1. Bar graph depicting quantitative results from gene expression analysis from heart lysates after 8 weeks of voluntary wheel running demonstrates significant downregulation specifically of HIPK1 (n = 3 mice per group, *p < 0.05, Student’s t test). f miR-222 inhibition during 8 weeks of voluntary wheel running leads to HIPK1 overexpression (n = 5 mice per group, *p < 0.05, Student’s t test). Error bars represent ± s.e.m