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

Author:

Nguyen Thuy-Hang1,Limpens Maelle1,Bouhmidi Sihame1,Paprzycki Lise1,Legrand Alexandre1,Declèves Anne-Emilie2ORCID,Heher Philipp3,Belayew Alexandra1ORCID,Banerji Christopher R. S.34,Zammit Peter S.3ORCID,Tassin Alexandra1ORCID

Affiliation:

1. Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium

2. Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium

3. Randall Centre for Cell and Molecular Biophysics, King’s College London, Guy’s Campus, London SE1 1UL, UK

4. The Alan Turing Institute, The British Library, London NW1 2DB, UK

Abstract

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.

Funder

Medical Research Council

Austrian Science Fund

FSH Research

French non-profit organization AMIS FSH

Fonds de la Recherche Scientifique—FNRS

Publisher

MDPI AG

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3