Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts
Tissue regeneration depends on the complex processes of angiogenesis, inflammation and wound healing. Regarding muscle tissue, glucocorticoids (GCs) inhibit pro-inflammatory signalling and angiogenesis and lead to muscle atrophy. Our hypothesis is that the synthetic GC dexamethasone (dex) impairs an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/7986 |
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| author | Eva K. Langendorf Pol M. Rommens Philipp Drees Ulrike Ritz |
| author_facet | Eva K. Langendorf Pol M. Rommens Philipp Drees Ulrike Ritz |
| author_sort | Eva K. Langendorf |
| collection | DOAJ |
| description | Tissue regeneration depends on the complex processes of angiogenesis, inflammation and wound healing. Regarding muscle tissue, glucocorticoids (GCs) inhibit pro-inflammatory signalling and angiogenesis and lead to muscle atrophy. Our hypothesis is that the synthetic GC dexamethasone (dex) impairs angiogenesis leading to muscle atrophy or inhibited muscle regeneration. Therefore, this study aims to elucidate the effect of dexamethasone on HUVECs under different conditions in mono- and co-culture with myoblasts to evaluate growth behavior and dex impact with regard to muscle atrophy and muscle regeneration. Viability assays, qPCR, immunofluorescence as well as ELISAs were performed on HUVECs, and human primary myoblasts seeded under different culture conditions. Our results show that dex had a higher impact on the tube formation when HUVECs were maintained with VEGF. Gene expression was not influenced by dex and was independent of cells growing in a 2D or 3D matrix. In co-culture CD31 expression was suppressed after incubation with dex and gene expression analysis revealed that dex enhanced expression of myogenic transcription factors, but repressed angiogenic factors. Moreover, dex inhibited the VEGF mediated pro angiogenic effect of myoblasts and inhibited expression of angiogenic inducers in the co-culture model. This is the first study describing a co-culture of human primary myoblast and HUVECs maintained under different conditions. Our results indicate that dex affects angiogenesis via inhibition of VEGF release at least in myoblasts, which could be responsible not only for the development of muscle atrophy after dex administration, but also for inhibition of muscle regeneration after vascular damage. |
| first_indexed | 2024-03-10T09:15:21Z |
| format | Article |
| id | doaj.art-ce3f0c7f2b0a4f78bb1825806727a05c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:15:21Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ce3f0c7f2b0a4f78bb1825806727a05c2023-11-22T05:41:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215798610.3390/ijms22157986Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human MyoblastsEva K. Langendorf0Pol M. Rommens1Philipp Drees2Ulrike Ritz3Department of Orthopedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Orthopedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Orthopedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Orthopedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyTissue regeneration depends on the complex processes of angiogenesis, inflammation and wound healing. Regarding muscle tissue, glucocorticoids (GCs) inhibit pro-inflammatory signalling and angiogenesis and lead to muscle atrophy. Our hypothesis is that the synthetic GC dexamethasone (dex) impairs angiogenesis leading to muscle atrophy or inhibited muscle regeneration. Therefore, this study aims to elucidate the effect of dexamethasone on HUVECs under different conditions in mono- and co-culture with myoblasts to evaluate growth behavior and dex impact with regard to muscle atrophy and muscle regeneration. Viability assays, qPCR, immunofluorescence as well as ELISAs were performed on HUVECs, and human primary myoblasts seeded under different culture conditions. Our results show that dex had a higher impact on the tube formation when HUVECs were maintained with VEGF. Gene expression was not influenced by dex and was independent of cells growing in a 2D or 3D matrix. In co-culture CD31 expression was suppressed after incubation with dex and gene expression analysis revealed that dex enhanced expression of myogenic transcription factors, but repressed angiogenic factors. Moreover, dex inhibited the VEGF mediated pro angiogenic effect of myoblasts and inhibited expression of angiogenic inducers in the co-culture model. This is the first study describing a co-culture of human primary myoblast and HUVECs maintained under different conditions. Our results indicate that dex affects angiogenesis via inhibition of VEGF release at least in myoblasts, which could be responsible not only for the development of muscle atrophy after dex administration, but also for inhibition of muscle regeneration after vascular damage.https://www.mdpi.com/1422-0067/22/15/7986dexamethasonehuman primary myoblastsHUVECsco-cultureCD31VEGF |
| spellingShingle | Eva K. Langendorf Pol M. Rommens Philipp Drees Ulrike Ritz Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts International Journal of Molecular Sciences dexamethasone human primary myoblasts HUVECs co-culture CD31 VEGF |
| title | Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts |
| title_full | Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts |
| title_fullStr | Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts |
| title_full_unstemmed | Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts |
| title_short | Dexamethasone Inhibits the Pro-Angiogenic Potential of Primary Human Myoblasts |
| title_sort | dexamethasone inhibits the pro angiogenic potential of primary human myoblasts |
| topic | dexamethasone human primary myoblasts HUVECs co-culture CD31 VEGF |
| url | https://www.mdpi.com/1422-0067/22/15/7986 |
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