Gene expression changes associated with the airway wall response to injury

Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. Only limited data is available in relation to in vivo characterisation of the molecular features of repair in the airway. This study sought to characterise the dynamic changes in gene expression that are associated with airway repair in response to physical injury. Gene expression changes in the airway wall following bronchial brush biopsy were profiled in anaesthetised sheep. The experimental design featured sequential studies in the same animals (n=8) over the course of a week and yielded data relating to the repair process 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 repair response included the up-regulation of cell cycle genes at d1 and d3, and the later pronounced up-regulation of extracellular matrix-related genes at d3 and d7. It is possible to follow the process of airway wall repair in 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. Keywords: response to airway injury Each sheep was subjected to a protocol which involved the procedure of endobronchial brush biopsy (BBr) being performed, under anaesthesia, on three occasions, with two separate airway sites being subjected to brushing on each occasion. Two sheep were subjected to BBr seven days, three days and six hours prior to euthanasia, two sheep at seven days, three days and one day prior to euthanasia, two sheep at seven days, one day and six hours prior to euthanasia and two sheep at three days, one day and six hours prior to euthanasia. At post mortem examination (PME) each time point was therefore represented by material derived from six sheep. Airway tissue from a naïve site (from a segment not subjected to BBr) was also collected from each sheep at necropsy.