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Journals / Türk Biyokimya Dergisi / 2021 / Cilt: 46 - Sayı: 4

Estradiol differentially regulates DUX4, β-catenin and PAX3/PAX7 in primary myoblasts of facioscapulohumeral muscular dystrophy patients

Hilmi UYSAL
Onur EROĞLU
Hacer KAYA
Ceren HANGÜL
Sibel BERKER KARAÜZÜM
Esin GÜVENİR ÇELİK
Pages
435–444
Publication Date
2022-11-06
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion: Our results suggest that estrogen might be a palliative treatment option via downregulation of DUX4 protein in DUX4 expressing FSHD patients.

📌 3 Key Takeaways

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Objective & Hypothesis:Objectives: There is a clinical variability and heterogeneity among Facioscapulohumeral Muscular Dystrophy (FSHD) patients.
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Key Findings & Data:In spite of few molecular studies supporting the protective role of estrogen in FSHD in vitro, there is no study revealing the effect of estradiol on the protein levels of DUX4, β-catenin and PAX3/PAX7.
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Conclusion & Impact:Conclusion: Our results suggest that estrogen might be a palliative treatment option via downregulation of DUX4 protein in DUX4 expressing FSHD patients.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Objectives: There is a clinical variability and heterogeneity among Facioscapulohumeral Muscular Dystrophy (FSHD) patients. Escalation after menopause in women, early onset in men suggests that estrogen might be a protective factor on the course of FSHD. In spite of few molecular studies supporting the protective role of estrogen in FSHD in vitro, there is no study revealing the effect of estradiol on the protein levels of DUX4, β-catenin and PAX3/PAX7. In present study, we investigated the effect of estradiol treatment on the expressions of DUX4, β-catenin and PAX3/PAX7 protein levels. Materials and Methods: Primary myoblasts of 63 and 71 years old (63yM/71yM) males; 47 years old (47yF) female FSHD patients were used. Cells were processed under these conditions; (i) untreated, (ii) 10 nM-30min estradiol and (iii) 10 nM-4 h estradiol treated. The expression of DUX4, PAX3/ PAX7 and β-catenin were examined by western-blotting. Results: Expression of DUX4 significantly downregulated after 4 h treatment of estradiol while PAX3/PAX7 56 kDa variant expression upregulated in 71yM cells. β-catenin and PAX3 expression was variable among the samples. Conclusion: Our results suggest that estrogen might be a palliative treatment option via downregulation of DUX4 protein in DUX4 expressing FSHD patients.

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Cite This Article

UYSAL, H., EROĞLU, O., KAYA, H., HANGÜL, C., KARAÜZÜM, S. B., ÇELİK, E. G. (2022). Estradiol differentially regulates DUX4, β-catenin and PAX3/PAX7 in primary myoblasts of facioscapulohumeral muscular dystrophy patients. Türk Biyokimya Dergisi, Cilt: 46 - Sayı: 4, 435–444. https://ajindex.com/articles/620721

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References (12)

  1. Hewitt JE, Lyle R, Clark LN, Valleley EM, Wright TJ, Wijmenga C, et al. Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum Mol Genet 1994; 3:1287–95
  2. Lemmers RJ, Wohlgemuth M, Frants RR, Padberg GW, Morava E, van der Maarel SM. Contractions of D4Z4 on 4qB subtelomeres do not cause facioscapulohumeral muscular dystrophy. Am J Hum Genet 2004;75:1124–30
  3. Lemmers RJ, Tawil R, Petek LM, Balog J, Block GJ, Santen GW, et al. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet 2012;44:1370–4
  4. Lyle R, Wright TJ, Clark LN, Hewitt JE. The FSHD-associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets of which are clustered on the short arms of the acrocentric chromosomes. Genomics 1995;28:389–97
  5. Bosnakovski D, Toso EA, Hartweck LM, Magli A, Lee HA, Thompson ER, et al. The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain. J Cell Sci 2017;130:3685–97
  6. Banerji CRS, Panamarova M, Hebaishi H, White RB, Relaix F, Severini S, et al. PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle. Nat Commun 2017;8:2152
  7. Banerji CRS, Zammit PS. PAX7 target gene repression is a superior FSHD biomarker than DUX4 target gene activation, associating with pathological severity and identifying FSHD at the single-cell level. Hum Mol Genet 2019;28:2224–36
  8. Osborne RJ, Welle S, Venance SL, Thornton CA, Tawil R. Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy. Neurology 2007;68: 569–77
  9. Cheli S, Francois S, Bodega B, Ferrari F, Tenedini E, Roncaglia E, et al. Expression profiling of FSHD-1 and FSHD-2 cells during myogenic differentiation evidences common and distinctive gene dysregulation patterns. PLoS One 2011;6:e20966
  10. Banerji CR, Knopp P, Moyle LA, Severini S, Orrell RW, Teschendorff AE, et al. Beta-catenin is central to DUX4-driven network rewiring in facioscapulohumeral muscular dystrophy. J R Soc Interface 2015;12:20140797
  11. Block GJ, Narayanan D, Amell AM, Petek LM, Davidson KC, Bird TD, et al. Wnt/beta-catenin signaling suppresses DUX4 expression and prevents apoptosis of FSHD muscle cells. Hum Mol Genet 2013;22:4661–72
  12. Giacoppo S, Thangavelu SR, Calabro RS, Bramanti P, Emanuela M. Role of Wnt/Β-catenin signaling in re