The University of Southampton
University of Southampton Institutional Repository

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

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

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.

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
0022-1007
2617-2633
Di Foggia, Valentina
2193926a-aed2-42bd-a873-026da4417f64
Zhang, Xinyu
3e311fbc-3210-4212-a092-ab5e09bbb315
Licastro, Danilo
7ce0ee62-6701-4afb-a82e-4e90a4ae02b4
Gerli, Mattia F M
d5e62de0-068c-457a-842b-fd4311ce1f63
Phadke, Rahul
ddd1d98b-41ac-456b-bb1b-34a895c30e3b
Muntoni, Francesco
24b9757d-8a5b-4532-94f6-6d25ba539ee7
Mourikis, Philippos
c224c6f8-c9c1-4254-8de9-fbc7d3b2cb00
Tajbakhsh, Shahragim
1286ae21-1c33-4fb8-92d5-fd0c0b110dcf
Ellis, Matthew
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Greaves, Laura C
e9eaaca4-e485-453c-a27f-87ff967e1759
Taylor, Robert W
094ef050-e4ce-4394-a68f-35b58255104d
Cossu, Giulio
d38cc5d6-3c91-4e06-92fd-b0016b06cd37
Robson, Lesley G
11c87a03-9c43-43f1-988e-7ffb07ff93ff
Marino, Silvia
74663155-292a-4741-9887-4d09d16658b3
Di Foggia, Valentina
2193926a-aed2-42bd-a873-026da4417f64
Zhang, Xinyu
3e311fbc-3210-4212-a092-ab5e09bbb315
Licastro, Danilo
7ce0ee62-6701-4afb-a82e-4e90a4ae02b4
Gerli, Mattia F M
d5e62de0-068c-457a-842b-fd4311ce1f63
Phadke, Rahul
ddd1d98b-41ac-456b-bb1b-34a895c30e3b
Muntoni, Francesco
24b9757d-8a5b-4532-94f6-6d25ba539ee7
Mourikis, Philippos
c224c6f8-c9c1-4254-8de9-fbc7d3b2cb00
Tajbakhsh, Shahragim
1286ae21-1c33-4fb8-92d5-fd0c0b110dcf
Ellis, Matthew
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Greaves, Laura C
e9eaaca4-e485-453c-a27f-87ff967e1759
Taylor, Robert W
094ef050-e4ce-4394-a68f-35b58255104d
Cossu, Giulio
d38cc5d6-3c91-4e06-92fd-b0016b06cd37
Robson, Lesley G
11c87a03-9c43-43f1-988e-7ffb07ff93ff
Marino, Silvia
74663155-292a-4741-9887-4d09d16658b3

Di Foggia, Valentina, Zhang, Xinyu, Licastro, Danilo, Gerli, Mattia F M, Phadke, Rahul, Muntoni, Francesco, Mourikis, Philippos, Tajbakhsh, Shahragim, Ellis, Matthew, Greaves, Laura C, Taylor, Robert W, Cossu, Giulio, Robson, Lesley G and Marino, Silvia (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), 2617-2633. (doi:10.1084/jem.20140317).

Record type: Article

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.

This record has no associated files available for download.

More information

Published date: 1 December 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

Identifiers

Local EPrints ID: 428173
URI: http://eprints.soton.ac.uk/id/eprint/428173
ISSN: 0022-1007
PURE UUID: f07bbfce-40db-4c8c-846d-441f763446d6

Catalogue record

Date deposited: 13 Feb 2019 17:30
Last modified: 10 May 2024 16:58

Export record

Altmetrics

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×