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Gene expression changes associated with the airway wall response to injury

ABSTRACT: 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

ORGANISM(S): Ovis aries

PROVIDER: GSE37086 | GEO | 2013/05/27

SECONDARY ACCESSION(S): PRJNA158297

REPOSITORIES: GEO

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Project description: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 naM-CM-/ve site (from a segment not subjected to BBr) was also collected from each sheep at necropsy.

Project description:Responses of the Human Airway Epithelium Transcriptome to In Vivo Injury; To identify genes participating in repair of the human airway epithelium following injury, we used bronchoscopy and brushing to denude the airway epithelium of healthy individuals, sequentially sampled the same region 7 and 14 days later, and assessed the recovered epithelium for relative levels of gene expression using Affymetrix high-density oligonucleotide microarrays with TaqMan PCR confirmation. Histologic assessment showed that the epithelium was denuded immediately following injury, at 7 days the epithelium was completely covered but partially de-differentiated, and by 14 days there was close to normal proportions of differentiated cells. Gene expression analysis was carried out with both the Affymetrix Microarray Suite 5.0 and Robust Multi-array Average algorithms, applying a multiple test correction to identify bona fide changes in gene expression. At day 7, there were substantial differences in the gene expression pattern compared to the resting epithelium, with a distinctive airway epithelial â??repair transcriptomeâ?? of actively proliferating cells in the process of re-differentiation. The repair transcriptome at 7 days was dominated by genes encoding proteins involved in cell cycle regulation, transcription, signal transduction, metabolism and transport. Interestingly, the majority of cell cycle genes differentially expressed at day 7 belonged to the G2 and M late phases of the cell cycle, suggesting that the proliferating cells are relatively synchronized 1 wk following injury. At 14 days post-injury, the majority of the gene expression changes observed at day 7 were no longer observed, with the expression profile similar to that of resting airway epithelium. Using a class prediction algorithm, a group of 50 genes dominated by cell cycle genes, that represent a human airway epithelial â??repair signatureâ?? was identified. These observations provide a baseline of the functional gene categories participating in the process of normal human airway epithelial repair that can be used in future studies of injury and repair in human airway epithelial diseases. Experiment Overall Design: comparison of gene expression in airway epithelial cells of the large airways, before and after mechanical injury caused by airway brushing

Project description:Responses of the Human Airway Epithelium Transcriptome to In Vivo Injury To identify genes participating in repair of the human airway epithelium following injury, we used bronchoscopy and brushing to denude the airway epithelium of healthy individuals, sequentially sampled the same region 7 and 14 days later, and assessed the recovered epithelium for relative levels of gene expression using Affymetrix high-density oligonucleotide microarrays with TaqMan PCR confirmation. Histologic assessment showed that the epithelium was denuded immediately following injury, at 7 days the epithelium was completely covered but partially de-differentiated, and by 14 days there was close to normal proportions of differentiated cells. Gene expression analysis was carried out with both the Affymetrix Microarray Suite 5.0 and Robust Multi-array Average algorithms, applying a multiple test correction to identify bona fide changes in gene expression. At day 7, there were substantial differences in the gene expression pattern compared to the resting epithelium, with a distinctive airway epithelial “repair transcriptome” of actively proliferating cells in the process of re-differentiation. The repair transcriptome at 7 days was dominated by genes encoding proteins involved in cell cycle regulation, transcription, signal transduction, metabolism and transport. Interestingly, the majority of cell cycle genes differentially expressed at day 7 belonged to the G2 and M late phases of the cell cycle, suggesting that the proliferating cells are relatively synchronized 1 wk following injury. At 14 days post-injury, the majority of the gene expression changes observed at day 7 were no longer observed, with the expression profile similar to that of resting airway epithelium. Using a class prediction algorithm, a group of 50 genes dominated by cell cycle genes, that represent a human airway epithelial “repair signature” was identified. These observations provide a baseline of the functional gene categories participating in the process of normal human airway epithelial repair that can be used in future studies of injury and repair in human airway epithelial diseases. Keywords: response to airway injury

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Gene expression changes associated with the airway wall response to injury

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