Academic Journal
Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy
| العنوان: | Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy |
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| المؤلفون: | Karpukhina, Anna, Galkin, Ivan, Ma, Yinxing, Dib, Carla, Zinovkin, Roman, Pletjushkina, Olga, Chernyak, Boris, Popova, Ekaterina, Vassetzky, Yegor |
| المساهمون: | Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Koltzov Institute of Developmental Biology, Russian Academy of Science (RAS), Lomonosov Moscow State University = Université d'État Lomonossov de Moscou Moscou (MSU), Belozersky Institute of Physico-Chemical Biology |
| المصدر: | ISSN: 2213-2317 ; Redox Biology ; https://hal.science/hal-03375945 ; Redox Biology, 2021, 43, pp.102008. ⟨10.1016/j.redox.2021.102008⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | DUX4, FSHD, Oxidative stress, Mitochondrial ROS, Muscle differentiation, PITX1, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] |
| الوصف: | International audience ; Muscles of patients with facioscapulohumeral dystrophy (FSHD) are characterized by sporadic DUX4 expression and oxidative stress which is at least partially induced by DUX4 protein. Nevertheless, targeting oxidative stress with antioxidants has a limited impact on FSHD patients, and the exact role of oxidative stress in the pathology of FSHD, as well as its interplay with the DUX4 expression, remain unclear. Here we set up a screen for genes that are upregulated by DUX4 via oxidative stress with the aim to target these genes rather than the oxidative stress itself. Immortalized human myoblasts expressing DUX4 (MB135-DUX4) have an increased level of reactive oxygen species (ROS) and exhibit differentiation defects which can be reduced by treating the cells with classic (Tempol) or mitochondria-targeted antioxidants (SkQ1). The transcriptome analysis of antioxidant-treated MB135 and MB135-DUX4 myoblasts allowed us to identify 200 genes with expression deregulated by DUX4 but normalized upon antioxidant treatment. Several of these genes, including PITX1, have been already associated with FSHD and/or muscle differentiation. We confirmed that PITX1 was indeed deregulated in MB135-DUX4 cells and primary FSHD myoblasts and revealed a redox component in PITX1 regulation. PITX1 silencing partially reversed the differentiation defects of MB135-DUX4 myoblasts. Our approach can be used to identify and target redox-dependent genes involved in human diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1016/j.redox.2021.102008 |
| الاتاحة: | https://hal.science/hal-03375945 https://hal.science/hal-03375945v1/document https://hal.science/hal-03375945v1/file/2021%20Karpukhina%20RB.pdf https://doi.org/10.1016/j.redox.2021.102008 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.2324B999 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.redox.2021.102008 |
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