Stefanski Adrianne L, Raclawska Dorota S, Evans Christopher M
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver School of Medicine, Aurora, CO, USA.
Methods Mol Biol. 2018;1809:169-201. doi: 10.1007/978-1-4939-8570-8_14.
In the lungs, the epithelium is a first line of innate defense. In acute settings, such as infection or particulate exposure, the epithelium is protective. Protection is conferred by the epithelium's role as a physical barrier and by its ability to synthesize proteins that promote defense directly through physical interactions (e.g., mucins and anti-microbial peptides) and indirectly through the production of proteins that regulate inflammation (e.g., cytokines and chemokines). Despite its importance as a first line of host defense, the epithelium is also a significant target and an effector in lung pathologies. Accordingly, to determine the significance and biological mechanisms of genes involved in pulmonary defense, it is important to be able to interrogate the lung epithelium. In mice, this presents challenges related to the cellular location and timing of interventions. Effective genetic strategies for targeting the lung epithelium using tissue-/cell-specific and inducible control have been developed over the past decade. Methods for spatiotemporal targeting of gene expression are described here.
在肺部，上皮组织是先天性防御的第一道防线。在急性情况下，如感染或接触颗粒物时，上皮组织具有保护作用。这种保护作用是由上皮组织作为物理屏障的作用以及其合成蛋白质的能力赋予的，这些蛋白质通过物理相互作用（如粘蛋白和抗菌肽）直接促进防御，并通过产生调节炎症的蛋白质（如细胞因子和趋化因子）间接促进防御。尽管上皮组织作为宿主防御的第一道防线很重要，但它也是肺部疾病的重要靶点和效应器。因此，为了确定参与肺部防御的基因的重要性和生物学机制，能够对肺上皮组织进行研究很重要。在小鼠中，这带来了与干预的细胞位置和时间相关的挑战。在过去十年中，已经开发出了使用组织/细胞特异性和诱导性控制来靶向肺上皮组织的有效基因策略。本文描述了基因表达时空靶向的方法。
