Chronic obstructive pulmonary disease (COPD) can sometimes be associated with skeletal muscle atrophy. Hypoxemic episodes, which occur during disease exacerbation and daily physical activity, are frequent in COPD patients. However, the link between hypoxemia and muscle atrophy remains unclear, along with mechanisms of muscle hypoxic stress response. Myogenic progenitors (MPs) and fibro/adipogenic progenitors (FAPs) express CD34 and participate to muscle mass maintenance. Although there is evidence linking CD34 expression and muscle repair, the link between CD34 expression, muscle wasting and the hypoxic stress observed in COPD has never been studied. Using a 2-day model of exposure to hypoxic conditions, we investigated the impact of hypoxia on skeletal muscle wasting and function, and elucidated the importance of CD34 expression in that response. A 2-day exposure to hypoxic conditions induces muscle atrophy, which was significantly worse in Cd34^−/− mice compared to wild type (WT). Moreover, the lack of CD34 expression negatively impacts the maximal strength of the extensor digitorum longus muscle in response to hypoxia. Following exposure to hypoxic conditions, FAPs (which support MPs differentiation and myogenesis) are significantly lower in Cd34^−/− mice compared to WT animals while the expression of myogenic regulatory factors and degradation factors (Atrogin) are similar. CD34 expression is important in the maintenance of muscle mass and function in response to hypoxic stress. These results highlight a new potential role for CD34 in muscle mass maintenance in hypoxic stress such as observed in COPD.

中文翻译：

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CD34调节骨骼肌对缺氧的反应。

慢性阻塞性肺疾病（COPD）有时可能与骨骼肌萎缩症相关。在COPD患者中，低氧血症发作通常在疾病恶化和日常体育活动中发生。然而，低氧血症和肌肉萎缩之间的联系以及肌肉低氧应激反应的机制仍然不清楚。成肌祖细胞（MPs）和纤维/成脂祖细胞（FAP）表达CD34并参与肌肉质量维持。尽管有证据表明CD34表达与肌肉修复有关，但从未研究过COPD中CD34表达，肌肉消瘦和低氧应激之间的联系。使用暴露于缺氧条件下的2天模型，我们研究了缺氧对骨骼肌消耗和功能的影响，并阐明了CD34表达在该反应中的重要性。与野生型（WT）相比，Cd34 ^{- / -}小鼠。此外，CD34表达的缺乏不利地影响了缺氧时趾长指肌的最大力量。暴露于低氧条件后，与野生动物相比，Cd34 ^{- / -}小鼠的FAP（支持MP分化和肌发生）显着降低，而肌源性调节因子和降解因子（Atrogin）的表达相似。CD34表达对于维持低氧应激反应的肌肉质量和功能很重要。这些结果突显了CD34在低氧应激（如在COPD中观察到）的肌肉质量维持中的新潜在作用。