Muscular dystrophies are severe disorders due to mutations in structural genes, and are characterized by skeletal muscle wasting, compromised patient mobility, and respiratory functions. Although previous works suggested enhancing regeneration and muscle mass as therapeutic strategies, these led to no long-term benefits in humans. Mice lacking the transcription factor Nfix have delayed regeneration and a shift toward an oxidative fiber type. Here, we show that ablating or silencing the transcription factor Nfix ameliorates pathology in several forms of muscular dystrophy. Silencing Nfix in postnatal dystrophic mice, when the first signs of the disease already occurred, rescues the pathology and, conversely, Nfix overexpression in dystrophic muscles increases regeneration and markedly exacerbates the pathology. We therefore offer a proof of principle for a novel therapeutic approach for muscular dystrophies based on delaying muscle regeneration.

Silencing Nfix rescues muscular dystrophy by delaying muscle regeneration / G. Rossi, C. Bonfanti, S. Antonini, M. Bastoni, S. Monteverde, A. Innocenzi, M. Saclier, V. Taglietti, G. Messina. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:1(2017 Oct 20). [10.1038/s41467-017-01098-y]

Silencing Nfix rescues muscular dystrophy by delaying muscle regeneration

G. Rossi
Primo
;
C. Bonfanti
Secondo
;
S. Antonini;S. Monteverde;M. Saclier;V. Taglietti
Penultimo
;
G. Messina
Ultimo
Project Administration
2017

Abstract

Muscular dystrophies are severe disorders due to mutations in structural genes, and are characterized by skeletal muscle wasting, compromised patient mobility, and respiratory functions. Although previous works suggested enhancing regeneration and muscle mass as therapeutic strategies, these led to no long-term benefits in humans. Mice lacking the transcription factor Nfix have delayed regeneration and a shift toward an oxidative fiber type. Here, we show that ablating or silencing the transcription factor Nfix ameliorates pathology in several forms of muscular dystrophy. Silencing Nfix in postnatal dystrophic mice, when the first signs of the disease already occurred, rescues the pathology and, conversely, Nfix overexpression in dystrophic muscles increases regeneration and markedly exacerbates the pathology. We therefore offer a proof of principle for a novel therapeutic approach for muscular dystrophies based on delaying muscle regeneration.
chemistry (all); biochemistry, genetics and molecular biology (all); physics and astronomy (all)
Settore BIO/17 - Istologia
   Role of the transcription factor Nfix in muscle regeneration and muscular dystrophies (RegeneratioNfix)
   RegeneratioNfix
   EUROPEAN COMMISSION
   FP7
   280611
20-ott-2017
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/530805
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