Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice

Yiming Lin; Andrew McClennan; Lisa Hoffman

doi:10.3390/biomedicines11082265

Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice

Biomedicines. 2023 Aug 14;11(8):2265. doi: 10.3390/biomedicines11082265.

Authors

Yiming Lin^{1

2}, Andrew McClennan^{2

3}, Lisa Hoffman^{1

2

3}

Affiliations

¹ Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
² The Lawson Health Research Institute, London, ON N6C 2R5, Canada.
³ Department of Medical Biophysics, Western University, London, ON N6A 3K7, Canada.

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 aimed to characterize the Ang/Tie2 signaling pathway within the diaphragm muscle of mouse models of DMD. Utilizing ELISA, immunoblots, and RT-qPCR, we demonstrated that Ang1 was downregulated, while the antagonist angiopoietin 2 (Ang2) was upregulated, leading to a decreased Ang1/Ang2 ratio. This correlated with a reduction in the 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 the diaphragm muscle of DMD and further investigations may lead to new therapeutic interventions for DMD.

Keywords: Duchenne muscular dystrophy; Tie2; angiogenesis; angiopoietin; diaphragm.

Grants and funding

PJT-152990/CAPMC/ CIHR/Canada