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LSD1 inhibition circumvents glucocorticoid-induced muscle wasting of male mice.
Cai, Qingshuang; Sahu, Rajesh; Ueberschlag-Pitiot, Vanessa; Souali-Crespo, Sirine; Charvet, Céline; Silem, Ilyes; Cottard, Félicie; Ye, Tao; Taleb, Fatima; Metzger, Eric; Schuele, Roland; Billas, Isabelle M L; Laverny, Gilles; Metzger, Daniel; Duteil, Delphine.
Afiliação
  • Cai Q; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Sahu R; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Ueberschlag-Pitiot V; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Souali-Crespo S; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Charvet C; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Silem I; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Cottard F; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Ye T; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Taleb F; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Metzger E; Klinik für Urologie und Zentrale Klinische Forschung, Klinikum der Albert-Ludwigs-Universität Freiburg, D-79106, Freiburg, Germany.
  • Schuele R; Klinik für Urologie und Zentrale Klinische Forschung, Klinikum der Albert-Ludwigs-Universität Freiburg, D-79106, Freiburg, Germany.
  • Billas IML; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Laverny G; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Metzger D; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France.
  • Duteil D; Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104- UMR-S 1258, F-67400, Illkirch, France. duteild@igbmc.fr.
Nat Commun ; 15(1): 3563, 2024 Apr 26.
Article em En | MEDLINE | ID: mdl-38670969
ABSTRACT
Synthetic glucocorticoids (GC), such as dexamethasone, are extensively used to treat chronic inflammation and autoimmune disorders. However, long-term treatments are limited by various side effects, including muscle atrophy. GC activities are mediated by the glucocorticoid receptor (GR), that regulates target gene expression in various tissues in association with cell-specific co-regulators. Here we show that GR and the lysine-specific demethylase 1 (LSD1) interact in myofibers of male mice, and that LSD1 connects GR-bound enhancers with NRF1-associated promoters to stimulate target gene expression. In addition, we unravel that LSD1 demethylase activity is required for triggering starvation- and dexamethasone-induced skeletal muscle proteolysis in collaboration with GR. Importantly, inhibition of LSD1 circumvents muscle wasting induced by pharmacological levels of dexamethasone, without affecting their anti-inflammatory activities. Thus, our findings provide mechanistic insights into the muscle-specific GC activities, and highlight the therapeutic potential of targeting GR co-regulators to limit corticotherapy-induced side effects.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dexametasona / Atrofia Muscular / Receptores de Glucocorticoides / Músculo Esquelético / Histona Desmetilases / Glucocorticoides Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dexametasona / Atrofia Muscular / Receptores de Glucocorticoides / Músculo Esquelético / Histona Desmetilases / Glucocorticoides Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França