Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease.
Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease.
复制标题
短期暴露于间歇性缺氧导致慢性肺部疾病中基因表达的变化。
DOI：
10.7554/elife.63003
复制
发表时间：
2021-02-18
期刊：
影响因子：
7.7
通讯作者：
Smith DF
中科院分区：
文献类型：
--
作者：
Wu G;Lee YY;Gulla EM;Potter A;Kitzmiller J;Ruben MD;Salomonis N;Whitsett JA;Francey LJ;Hogenesch JB;Smith DF
阻塞性睡眠呼吸暂停（OSA）是由气道塌陷和间歇性缺氧（IH）引起的，并与许多健康并发症有关。虽然肺是第一个感觉到氧水平变化的器官，但对IH对肺缺氧诱导因子反应通路的影响知之甚少。我们假设暴露于IH会导致细胞特异性上调和下调不同的表达途径。我们确定了暴露于IH的小鼠肺部昼夜节律和免疫途径的变化。在所有的细胞类型中，内皮细胞表现出最突出的转录变化。肌成纤维细胞中上调的基因富含与肺动脉高压相关的基因，包括目前用于治疗慢性肺部疾病的几种药物的靶点。更好地了解与OSA相关的疾病的病理生理机制可以改善我们的治疗方法，将治疗导向最相关的细胞和分子途径。
Obstructive sleep apnea (OSA) results from episodes of airway collapse and intermittent hypoxia (IH) and is associated with a host of health complications. Although the lung is the first organ to sense changes in oxygen levels, little is known about the consequences of IH to the lung hypoxia-inducible factor-responsive pathways. We hypothesized that exposure to IH would lead to cell-specific up- and downregulation of diverse expression pathways. We identified changes in circadian and immune pathways in lungs from mice exposed to IH. Among all cell types, endothelial cells showed the most prominent transcriptional changes. Upregulated genes in myofibroblast cells were enriched for genes associated with pulmonary hypertension and included targets of several drugs currently used to treat chronic pulmonary diseases. A better understanding of the pathophysiologic mechanisms underlying diseases associated with OSA could improve our therapeutic approaches, directing therapies to the most relevant cells and molecular pathways.