Cluster for Regenerative Medicine, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Bandar Putra Bertam, Kepala Batas, Penang, Malaysia.
PLoS One. 2013 Apr 9;8(4):e58930. doi: 10.1371/journal.pone.0058930. Print 2013.
Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. As only limited data is available in relation to the in vivo characterisation of the molecular features of repair in the airway we sought to characterise the dynamic changes in gene expression that are associated with the early response to physical injury in the airway wall.
METHODOLOGY/PRINCIPAL FINDINGS: We profiled gene expression changes in the airway wall using a large animal model of physical injury comprising bronchial brush biopsy in anaesthetised sheep. The experimental design featured sequential studies in the same animals over the course of a week and yielded data relating to the response at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the response included the up-regulation of cell cycle genes at d1 and d3, and the latter pronounced up-regulation of extracellular matrix-related genes at d3 and d7.
CONCLUSIONS/SIGNIFICANCE: It is possible to follow the airway wall response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance.
了解气道在受伤后的愈合方式对于剖析气道疾病病理学的机制至关重要。由于关于气道修复分子特征的体内特征仅有限的数据可用，因此我们试图描述与气道壁物理损伤早期反应相关的基因表达的动态变化。
方法/主要发现：我们使用包括麻醉绵羊支气管刷活检在内的物理损伤大动物模型，对气道壁的基因表达变化进行了分析。该实验设计采用了同一动物在一周内的序贯研究，获得了与损伤后 6 小时、1 天、3 天和 7 天的反应相关的数据。转录反应的显著特征包括与血管生成和免疫细胞激活、选择和分化相关的早期和持续下调基因的优势。反应的后期特征包括 d1 和 d3 时细胞周期基因的上调，以及 d3 和 d7 时细胞外基质相关基因的显著上调。
结论/意义：可以在同一动物身上随时间跟踪气道壁对物理损伤的反应。转录变化以可重复的方式在动物内部和之间协调表达功能相关基因。这种特征将为评估与比较相关的气道疾病病理学伴随的干扰提供基础。
