Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles

E. Fiacco, F. Castagnetti, V. Bianconi, L. Madaro, M. de Bardi, F. Nazio, A. D'Amico, E. Bertini, F. Cecconi, P. L. Puri, L. Latella

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a ‘disease modifier’ targeted by interventions aimed to promote regeneration and delay disease progression in DMD.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.70.

Original languageEnglish
JournalCell Death and Differentiation
DOIs
Publication statusAccepted/In press - Jul 22 2016

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Autophagy
Duchenne Muscular Dystrophy
Muscles
Regeneration
Inbred mdx Mouse
Disease Progression
Muscle Development
Muscle Cells
Publications
Cell Differentiation
Skeletal Muscle
Homeostasis
Fibrosis
Cell Death
Pharmacology
Wounds and Injuries

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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title = "Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles",
abstract = "Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a ‘disease modifier’ targeted by interventions aimed to promote regeneration and delay disease progression in DMD.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.70.",
author = "E. Fiacco and F. Castagnetti and V. Bianconi and L. Madaro and {de Bardi}, M. and F. Nazio and A. D'Amico and E. Bertini and F. Cecconi and Puri, {P. L.} and L. Latella",
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T1 - Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles

AU - Fiacco, E.

AU - Castagnetti, F.

AU - Bianconi, V.

AU - Madaro, L.

AU - de Bardi, M.

AU - Nazio, F.

AU - D'Amico, A.

AU - Bertini, E.

AU - Cecconi, F.

AU - Puri, P. L.

AU - Latella, L.

PY - 2016/7/22

Y1 - 2016/7/22

N2 - Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a ‘disease modifier’ targeted by interventions aimed to promote regeneration and delay disease progression in DMD.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.70.

AB - Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a ‘disease modifier’ targeted by interventions aimed to promote regeneration and delay disease progression in DMD.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.70.

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