Nrf2 augments skeletal muscle regeneration after ischaemia–reperfusion injury |
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| Authors: | Othman Al‐Sawaf Athanassios Fragoulis Christian Rosen Nora Keimes Elisa Anamaria Liehn Frank Hölzle Yuet Wai Kan Thomas Pufe Christoph Jan Wruck |
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| Affiliation: | 1. Department of Anatomy and Cell Biology, University Hospital, RWTH Aachen University, , Germany;2. Institute for Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, , Germany;3. Department of Oral and Maxillofacial Surgery, University Hospital, RWTH Aachen University, , Germany;4. Department of Laboratory Medicine, University of California, , San Francisco, CA, USA |
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| Abstract: | Skeletal muscles harbour a resident population of stem cells, termed satellite cells (SCs). After trauma, SCs leave their quiescent state to enter the cell cycle and undergo multiple rounds of proliferation, a process regulated by MyoD. To initiate differentiation, fusion and maturation to new skeletal muscle fibres, SCs up‐regulate myogenin. However, the regulation of these myogenic factors is not fully understood. In this study we demonstrate that Nrf2, a major regulator of oxidative stress defence, plays a role in the expression of these myogenic factors. In both promoter studies with myoblasts and a mouse model of muscle injury in Nrf2‐deficient mice, we show that Nrf2 prolongs SC proliferation by up‐regulating MyoD and suppresses SC differentiation by down‐regulating myogenin. Moreover, we show that IL‐6 and HGF, both factors that facilitate SC activation, induce Nrf2 activity in myoblasts. Thus, Nrf2 activity promotes muscle regeneration by modulating SC proliferation and differentiation and thereby provides implications for tissue regeneration.Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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| Keywords: | Nrf2 MyoD ischaemia– reperfusion injury skeletal muscle |
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