Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice
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...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/8/2265 |
| _version_ | 1797435959307927552 |
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| author | Yiming Lin Andrew McClennan Lisa Hoffman |
| author_facet | Yiming Lin Andrew McClennan Lisa Hoffman |
| author_sort | Yiming Lin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:55:46Z |
| format | Article |
| id | doaj.art-e5260e0393a54ff9b63836fff734d080 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:55:46Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-e5260e0393a54ff9b63836fff734d0802023-12-01T01:41:37ZengMDPI AGBiomedicines2227-90592023-08-01118226510.3390/biomedicines11082265Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD MiceYiming Lin0Andrew McClennan1Lisa Hoffman2Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, CanadaThe Lawson Health Research Institute, London, ON N6C 2R5, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, CanadaIn 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.https://www.mdpi.com/2227-9059/11/8/2265Duchenne muscular dystrophyangiopoietinTie2angiogenesisdiaphragm |
| spellingShingle | Yiming Lin Andrew McClennan Lisa Hoffman Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice Biomedicines Duchenne muscular dystrophy angiopoietin Tie2 angiogenesis diaphragm |
| title | Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice |
| title_full | Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice |
| title_fullStr | Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice |
| title_full_unstemmed | Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice |
| title_short | Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice |
| title_sort | characterization of the ang tie2 signaling pathway in the diaphragm muscle of dmd mice |
| topic | Duchenne muscular dystrophy angiopoietin Tie2 angiogenesis diaphragm |
| url | https://www.mdpi.com/2227-9059/11/8/2265 |
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