Characterization of the Ang/Tie2 Signaling Pathway in the Skeletal Muscle of DMD
Abstract
In Duchenne muscular dystrophy (DMD), angiogenesis appears to be attenuated. Local administration of angiopoietin 1 (Ang1) has been shown to reduce inflammation, ischemia, and fibrosis in DMD mice. Ang1 is a vital vascular stabilizing factor that activates the endothelial cell receptor Tie2, leading to downstream pro-survival PI3K/Akt pathway activation and eNOS phosphorylation. In this study, we aim to characterize the Ang/Tie2 signaling pathway within the skeletal muscle of mouse models of DMD. Utilizing immunoblots and RT-qPCR, we show that Ang1 is downregulated, while the antagonist angiopoietin 2 (Ang2) is upregulated, leading to a decreased Ang1/Ang2 ratio. This correlates with a reduction in phosphorylated Tie2/total Tie2 ratio. Interestingly, no significant differences in Akt or eNOS phosphorylation were observed, although DMD murine models did have elevated total Akt protein concentrations. These observations suggest that Ang1/Tie2 signaling may be dysregulated in DMD and further investigations may lead to new therapeutic interventions for DMD.