title: Nrf2 augments skeletal muscle regeneration after ischaemia-reperfusion injury.
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.
authors.affiliation: Department of Anatomy and Cell Biology, University Hospital, RWTH Aachen University, Germany.
authors.forename: Othman
authors.initials: O
authors.lastname: Al-Sawaf
authors.forename: Athanassios
authors.initials: A
authors.lastname: Fragoulis
authors.forename: Christian
authors.initials: C
authors.lastname: Rosen
authors.forename: Nora
authors.initials: N
authors.lastname: Keimes
authors.forename: Elisa Anamaria
authors.initials: EA
authors.lastname: Liehn
authors.forename: Frank
authors.initials: F
authors.lastname: Hölzle
authors.forename: Yuet Wai
authors.initials: YW
authors.lastname: Kan
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.forename: Tolga Taha
authors.initials: TT
authors.lastname: Sönmez
authors.forename: Christoph Jan
authors.initials: CJ
authors.lastname: Wruck
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012038:Regeneration / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*; D014162:Transfection
chemical_list: D017570:MyoD Protein; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse
keywords: MyoD; Nrf2; ischaemia-reperfusion injury; skeletal muscle