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SETDB1 modulates the TGFß response in Duchenne muscular dystrophy myotubes.
Granados, Alice; Zamperoni, Maeva; Rapone, Roberta; Moulin, Maryline; Boyarchuk, Ekaterina; Bouyioukos, Costas; Del Maestro, Laurence; Joliot, Véronique; Negroni, Elisa; Mohamed, Myriame; Piquet, Sandra; Bigot, Anne; Le Grand, Fabien; Albini, Sonia; Ait-Si-Ali, Slimane.
Afiliación
  • Granados A; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Zamperoni M; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Rapone R; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Moulin M; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Boyarchuk E; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Bouyioukos C; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Del Maestro L; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Joliot V; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Negroni E; Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France.
  • Mohamed M; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Piquet S; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Bigot A; Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France.
  • Le Grand F; Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315, Institut NeuroMyoGène, Pathophysiology and Genetics of Neuron and Muscle (PGNM) Unit, 69008 Lyon, France.
  • Albini S; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
  • Ait-Si-Ali S; Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.
Sci Adv ; 10(18): eadj8042, 2024 May 03.
Article en En | MEDLINE | ID: mdl-38691608
ABSTRACT
Overactivation of the transforming growth factor-ß (TGFß) signaling in Duchenne muscular dystrophy (DMD) is a major hallmark of disease progression, leading to fibrosis and muscle dysfunction. Here, we investigated the role of SETDB1 (SET domain, bifurcated 1), a histone lysine methyltransferase involved in muscle differentiation. Our data show that, following TGFß induction, SETDB1 accumulates in the nuclei of healthy myotubes while being already present in the nuclei of DMD myotubes where TGFß signaling is constitutively activated. Transcriptomics revealed that depletion of SETDB1 in DMD myotubes leads to down-regulation of TGFß target genes coding for secreted factors involved in extracellular matrix remodeling and inflammation. Consequently, SETDB1 silencing in DMD myotubes abrogates the deleterious effect of their secretome on myoblast differentiation by impairing myoblast pro-fibrotic response. Our findings indicate that SETDB1 potentiates the TGFß-driven fibrotic response in DMD muscles, providing an additional axis for therapeutic intervention.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transducción de Señal / Factor de Crecimiento Transformador beta / N-Metiltransferasa de Histona-Lisina / Fibras Musculares Esqueléticas / Distrofia Muscular de Duchenne Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transducción de Señal / Factor de Crecimiento Transformador beta / N-Metiltransferasa de Histona-Lisina / Fibras Musculares Esqueléticas / Distrofia Muscular de Duchenne Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article