Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy

Valentina Di Foggia; Xinyu Zhang; Danilo Licastro; Mattia F M Gerli; Rahul Phadke; Francesco Muntoni; Philippos Mourikis; Shahragim Tajbakhsh; Matthew Ellis; Laura C Greaves; Robert W Taylor; Giulio Cossu; Lesley G Robson; Silvia Marino

doi:10.1084/jem.20140317

Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy

Valentina Di Foggia, Xinyu Zhang, Danilo Licastro, Mattia F M Gerli, Rahul Phadke, Francesco Muntoni, Philippos Mourikis, Shahragim Tajbakhsh, Matthew Ellis, Laura C Greaves, Robert W Taylor, Giulio Cossu, Lesley G Robson, Silvia Marino

Division of Cell Matrix Biology & Regenerative Medicine (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.

Original language	English
Pages (from-to)	2617-33
Number of pages	17
Journal	The Journal of experimental medicine
Volume	211
Issue number	13
DOIs	https://doi.org/10.1084/jem.20140317
Publication status	Published - 15 Dec 2014

Keywords

Animals
Cell Differentiation
Chronic Disease
DNA Damage
Disease Models, Animal
Gene Expression Profiling
Gene Expression Regulation
Humans
Macular Degeneration
Metallothionein
Mice, Inbred mdx
Mice, Transgenic
Muscle Development
Muscle Strength
Muscle, Skeletal
Oxidative Stress
PAX7 Transcription Factor
Polycomb Repressive Complex 1
Proto-Oncogene Proteins
Reactive Oxygen Species
Regeneration
Reproducibility of Results
Satellite Cells, Skeletal Muscle
Systems Biology
Journal Article
Research Support, Non-U.S. Gov't

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10.1084/jem.20140317

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Di Foggia, V., Zhang, X., Licastro, D., Gerli, M. F. M., Phadke, R., Muntoni, F., Mourikis, P., Tajbakhsh, S., Ellis, M., Greaves, L. C., Taylor, R. W., Cossu, G., Robson, L. G., & Marino, S. (2014). Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy. The Journal of experimental medicine, 211(13), 2617-33. https://doi.org/10.1084/jem.20140317

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title = "Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy",

abstract = "The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.",

keywords = "Animals, Cell Differentiation, Chronic Disease, DNA Damage, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Humans, Macular Degeneration, Metallothionein, Mice, Inbred mdx, Mice, Transgenic, Muscle Development, Muscle Strength, Muscle, Skeletal, Oxidative Stress, PAX7 Transcription Factor, Polycomb Repressive Complex 1, Proto-Oncogene Proteins, Reactive Oxygen Species, Regeneration, Reproducibility of Results, Satellite Cells, Skeletal Muscle, Systems Biology, Journal Article, Research Support, Non-U.S. Gov't",

author = "{Di Foggia}, Valentina and Xinyu Zhang and Danilo Licastro and Gerli, {Mattia F M} and Rahul Phadke and Francesco Muntoni and Philippos Mourikis and Shahragim Tajbakhsh and Matthew Ellis and Greaves, {Laura C} and Taylor, {Robert W} and Giulio Cossu and Robson, {Lesley G} and Silvia Marino",

note = "{\textcopyright} 2014 Di Foggia et al.",

year = "2014",

month = dec,

day = "15",

doi = "10.1084/jem.20140317",

language = "English",

volume = "211",

pages = "2617--33",

journal = "The Journal of experimental medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

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Di Foggia, V, Zhang, X, Licastro, D, Gerli, MFM, Phadke, R, Muntoni, F, Mourikis, P, Tajbakhsh, S, Ellis, M, Greaves, LC, Taylor, RW, Cossu, G, Robson, LG & Marino, S 2014, 'Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy', The Journal of experimental medicine, vol. 211, no. 13, pp. 2617-33. https://doi.org/10.1084/jem.20140317

TY - JOUR

T1 - Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy

AU - Di Foggia, Valentina

AU - Zhang, Xinyu

AU - Licastro, Danilo

AU - Gerli, Mattia F M

AU - Phadke, Rahul

AU - Muntoni, Francesco

AU - Mourikis, Philippos

AU - Tajbakhsh, Shahragim

AU - Ellis, Matthew

AU - Greaves, Laura C

AU - Taylor, Robert W

AU - Cossu, Giulio

AU - Robson, Lesley G

AU - Marino, Silvia

PY - 2014/12/15

Y1 - 2014/12/15

N2 - The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.

AB - The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.

KW - Animals

KW - Cell Differentiation

KW - Chronic Disease

KW - DNA Damage

KW - Disease Models, Animal

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Humans

KW - Macular Degeneration

KW - Metallothionein

KW - Mice, Inbred mdx

KW - Mice, Transgenic

KW - Muscle Development

KW - Muscle Strength

KW - Muscle, Skeletal

KW - Oxidative Stress

KW - PAX7 Transcription Factor

KW - Polycomb Repressive Complex 1

KW - Proto-Oncogene Proteins

KW - Reactive Oxygen Species

KW - Regeneration

KW - Reproducibility of Results

KW - Satellite Cells, Skeletal Muscle

KW - Systems Biology

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1084/jem.20140317

DO - 10.1084/jem.20140317

M3 - Article

C2 - 25452464

SN - 0022-1007

VL - 211

SP - 2617

EP - 2633

JO - The Journal of experimental medicine

JF - The Journal of experimental medicine

IS - 13

ER -

Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy

Abstract

Keywords

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