Nrf2 augments skeletal muscle regeneration after ischaemia-reperfusion injury
Nrf2 augments skeletal muscle regeneration after ischaemia-reperfusion injury
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DOI：
10.1002/path.4418
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发表时间：
2014-12-01
影响因子：
7.3
通讯作者：
Wruck, Christoph Jan
中科院分区：
文献类型：
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作者：
Al-Sawaf, Othman;Fragoulis, Athanassios;Wruck, Christoph Jan
骨骼肌中有一群干细胞，称为卫星细胞（SC）。创伤后，SC离开其静止状态进入细胞周期并经历多轮增殖，这是一个由MyoD调节的过程。为了启动分化、融合和成熟为新的骨骼肌纤维，SC上调肌细胞生成素。然而，这些生肌因子的调节尚未完全了解。在这项研究中，我们证明了Nrf 2，氧化应激防御的主要调节剂，在这些生肌因子的表达中发挥作用。在成肌细胞和Nrf 2缺陷小鼠肌肉损伤小鼠模型的启动子研究中，我们发现Nrf 2通过上调MyoD抑制SC增殖，通过下调肌细胞生成素抑制SC分化。此外，我们表明，IL-6和HGF，这两个因素，促进SC激活，诱导成肌细胞中的Nrf 2活性。因此，Nrf 2活性通过调节SC增殖和分化促进肌肉再生，从而为组织再生提供启示。由John Wiley & Sons有限公司出版
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 (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.