The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected
FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders and is linked to the inappropriate expression of the DUX4 transcription factor in skeletal muscles. The deregulated molecular network causing FSHD muscle dysfunction and pathology is not well unders...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3327 |
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| author | Thuy-Hang Nguyen Maelle Limpens Sihame Bouhmidi Lise Paprzycki Alexandre Legrand Anne-Emilie Declèves Philipp Heher Alexandra Belayew Christopher R. S. Banerji Peter S. Zammit Alexandra Tassin |
| author_facet | Thuy-Hang Nguyen Maelle Limpens Sihame Bouhmidi Lise Paprzycki Alexandre Legrand Anne-Emilie Declèves Philipp Heher Alexandra Belayew Christopher R. S. Banerji Peter S. Zammit Alexandra Tassin |
| author_sort | Thuy-Hang Nguyen |
| collection | DOAJ |
| description | FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders and is linked to the inappropriate expression of the DUX4 transcription factor in skeletal muscles. The deregulated molecular network causing FSHD muscle dysfunction and pathology is not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4-induced cell death. In this study, we further explored the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knockdown in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches. |
| first_indexed | 2024-04-24T18:11:56Z |
| format | Article |
| id | doaj.art-f38a0076c826444eb8ce8da70e5120a5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:11:56Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f38a0076c826444eb8ce8da70e5120a52024-03-27T13:45:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256332710.3390/ijms25063327The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than ExpectedThuy-Hang Nguyen0Maelle Limpens1Sihame Bouhmidi2Lise Paprzycki3Alexandre Legrand4Anne-Emilie Declèves5Philipp Heher6Alexandra Belayew7Christopher R. S. Banerji8Peter S. Zammit9Alexandra Tassin10Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumLaboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumLaboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumLaboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumLaboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumDepartment of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumRandall Centre for Cell and Molecular Biophysics, King’s College London, Guy’s Campus, London SE1 1UL, UKLaboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumRandall Centre for Cell and Molecular Biophysics, King’s College London, Guy’s Campus, London SE1 1UL, UKRandall Centre for Cell and Molecular Biophysics, King’s College London, Guy’s Campus, London SE1 1UL, UKLaboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, BelgiumFacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders and is linked to the inappropriate expression of the DUX4 transcription factor in skeletal muscles. The deregulated molecular network causing FSHD muscle dysfunction and pathology is not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4-induced cell death. In this study, we further explored the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knockdown in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.https://www.mdpi.com/1422-0067/25/6/3327FSHDDUX4HIF1αmyogenesisskeletal muscle |
| spellingShingle | Thuy-Hang Nguyen Maelle Limpens Sihame Bouhmidi Lise Paprzycki Alexandre Legrand Anne-Emilie Declèves Philipp Heher Alexandra Belayew Christopher R. S. Banerji Peter S. Zammit Alexandra Tassin The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected International Journal of Molecular Sciences FSHD DUX4 HIF1α myogenesis skeletal muscle |
| title | The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected |
| title_full | The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected |
| title_fullStr | The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected |
| title_full_unstemmed | The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected |
| title_short | The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected |
| title_sort | dux4 hif1α axis in murine and human muscle cells a link more complex than expected |
| topic | FSHD DUX4 HIF1α myogenesis skeletal muscle |
| url | https://www.mdpi.com/1422-0067/25/6/3327 |
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