Cigarette smoke-induced airspace disease in mice develops independently of HIF-1α signaling in leukocytes.
Cigarette smoke-induced airspace disease in mice develops independently of HIF-1α signaling in leukocytes.
复制标题
香烟烟雾引起的小鼠空腔疾病的发展独立于白细胞中的 HIF-1α 信号传导。
DOI：
10.1152/ajplung.00491.2021
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Janssen,WilliamJ
中科院分区：
文献类型：
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作者：
Hume,PatrickS;McClendon,Jazalle;Kopf,KatrinaW;Harral,JulieW;Poczobutt,JoannaM;McCubbrey,AlexandraL;Smith,BradfordJ;Henson,PeterM;Majka,SusanM;Petrache,Irina;Janssen,WilliamJ
慢性阻塞性肺疾病（COPD）是一种主要由吸烟引起的流行性疾病，其发病机制尚未完全阐明。对人类和小鼠的研究表明，缺氧诱导因子-1 α（HIF-1α）可能发挥作用。肺内HIF-1α水平降低与血管密度降低相关，而白细胞HIF-1α水平升高可能是炎症增加的原因。为了阐明白细胞HIF-1α在COPD中的特异性作用，我们将白细胞中HIF-1α条件性缺失或过表达的转基因小鼠暴露于香烟烟雾中7个月。结果包括肺生理学、通过微计算机断层扫描获得的通气肺容量、肺形态学和组织学以及心肺血流动力学。总的来说，香烟烟雾增加了所有菌株的充气肺容量，准静态肺顺应性，吸气量，而减少了总的肺泡间隔容积。与烟雾暴露无关，与白细胞特异性HIF-1α缺失的小鼠相比，白细胞特异性HIF-1α过表达的小鼠具有增加的准静态顺应性，吸气量和肺泡间隔体积。然而，香烟烟雾诱导的肺部疾病的总体发展相对于任何条件菌株的对照小鼠没有变化。这表明小鼠香烟烟雾诱导的空域疾病的发生独立于白细胞HIF-1α信号传导。
The pathogenesis of chronic obstructive pulmonary disease (COPD), a prevalent disease primarily caused by cigarette smoke exposure, is incompletely elucidated. Studies in humans and mice have suggested that hypoxia-inducible factor-1α (HIF-1α) may play a role. Reduced lung levels of HIF-1α are associated with decreased vascular density, whereas increased leukocyte HIF-1α may be responsible for increased inflammation. To elucidate the specific role of leukocyte HIF-1α in COPD, we exposed transgenic mice with conditional deletion or overexpression of HIF-1α in leukocytes to cigarette smoke for 7 mo. Outcomes included pulmonary physiology, aerated lung volumes via microcomputed tomography, lung morphometry and histology, and cardiopulmonary hemodynamics. On aggregate, cigarette smoke increased the aerated lung volume, quasi-static lung compliance, inspiratory capacity of all strains while reducing the total alveolar septal volume. Independent of smoke exposure, mice with leukocyte-specific HIF-1α overexpression had increased quasi-static compliance, inspiratory capacity, and alveolar septal volume compared with mice with leukocyte-specific HIF-1α deletion. However, the overall development of cigarette smoke-induced lung disease did not vary relative to control mice for either of the conditional strains. This suggests that the development of murine cigarette smoke-induced airspace disease occurs independently of leukocyte HIF-1α signaling.