Fig. 5: Genome-wide gene profiling in GRK−β1AR TG and GRK−β1AR;miR-150 DTG mice identifies novel genes that are regulated by β1AR/β-arrestin-mediated signaling and are miR-150’s targets.
A, B Genome-wide profiling and filtering strategies of array dataset based on the correlation between transcript signatures and cardiac phenotypes. Sixteen dysregulated (DE) genes, which are upregulated in the I dataset (ISO GRK−β1AR TG compared to vehicle GRK−β1AR TG controls) but are downregulated in the II dataset (ISO GRK−β1AR;miR-150 DTG compared to ISO GRK−β1AR TG) at 1-week post-treatment, were chosen for additional analyses. Twenty other DE genes, which are downregulated in the I dataset (ISO GRK−β1AR TG compared to vehicle GRK−β1AR TG controls) but are upregulated in the II dataset (ISO GRK−β1AR;miR-150 DTG compared to ISO GRK−β1AR TG) at 1-week post-treatment, were chosen for further analyses. N = 3 per group. C–K Validation strategy of array dataset. Seven potentially deleterious DE genes (Cspg5, Cfl1, Gdap1l1, Mfsd12, Arhgef39, Map2k7, and Cdk14) were validated by QRT-PCR analyses in LVs from GRK−β1AR TG and GRK−β1AR;miR-150 DTG mice at 1-week post-treatment (D–J). The other potentially beneficial DE gene (Slitrk6) was validated by QRT-PCR analyses in LVs from GRK−β1AR TG and GRK−β1AR;miR-150 DTG mice at 1-week post-treatment (K). Of note, other genes are not validated as being dysregulated as shown in (B) or are undetectable in LVs. Data are presented as fold induction of gene expression normalized to Gapdh. N = 3 per group. Two-way ANOVA with Tukey multiple comparison test. *P < 0.05, **P < 0.01, or ***P < 0.001 vs. vehicle; #P < 0.05, ##P < 0.01, or ###P < 0.001 vs. ISO GRK−β1AR TG. All data are presented as mean ± SEM.
