The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex than Expected

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

doi:10.20944/preprints202211.0532.v3

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202211.0532.v3

Preprint Article Version 3 Preserved in Portico This version is not peer-reviewed

The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex than Expected

Christopher R. S. Banerji

Peter S. Zammit

Alexandra Tassin

Version 1 : Received: 24 November 2022 / Approved: 29 November 2022 / Online: 29 November 2022 (03:50:26 CET)
Version 2 : Received: 2 December 2022 / Approved: 5 December 2022 / Online: 5 December 2022 (02:01:31 CET)
Version 3 : Received: 26 January 2024 / Approved: 28 January 2024 / Online: 29 January 2024 (04:15:35 CET)

A peer-reviewed article of this Preprint also exists.

Nguyen, T.-H.; Limpens, M.; Bouhmidi, S.; Paprzycki, L.; Legrand, A.; Declèves, A.-E.; Heher, P.; Belayew, A.; Banerji, C.R.S.; Zammit, P.S.; et al. The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected. International Journal of Molecular Sciences 2024, 25, 3327, doi:10.3390/ijms25063327. Nguyen, T.-H.; Limpens, M.; Bouhmidi, S.; Paprzycki, L.; Legrand, A.; Declèves, A.-E.; Heher, P.; Belayew, A.; Banerji, C.R.S.; Zammit, P.S.; et al. The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected. International Journal of Molecular Sciences 2024, 25, 3327, doi:10.3390/ijms25063327.

Abstract

FacioScapuloHumeral Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders, and is linked to the inappropriate expression of the DUX4 transcription factor in adult muscles. The deregulated molecular network causing FSHD skeletal muscle dysfunction and pathology is still 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 explore 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 knock-down 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.

Keywords

FSHD; DUX4, HIF1α, myogenesis and skeletal muscle

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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