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Physiol. Genomics 29: 139-148, 2007. First published December 12, 2006; doi:10.1152/physiolgenomics.00167.2006 Free Article
1094-8341/07 $8.00
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Received 28 July 2006; accepted in final form 1 December 2006.
Physiological Genomics 29:139-148 (2007)
1094-8341/07 $8.00 © 2007 American Physiological Society

Responses of the human airway epithelium transcriptome to in vivo injury

Adriana Heguy, Ben-Gary Harvey, Philip L. Leopold, Igor Dolgalev, Tina Raman and Ronald G. Crystal

Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

To identify genes participating in human airway epithelial repair, 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 gene expression by Affymetrix microarrays with TaqMan RT-PCR confirmation. Histologically, the injured area was completely covered by a partially redifferentiated epithelial layer after 7 days; by 14 days the airway epithelium was very similar to the uninjured state. At day 7 compared with resting epithelium, there were substantial differences in gene expression pattern, with a distinctive airway epithelial "repair transcriptome" of actively proliferating cells in the process of redifferentiation. The repair transcriptome at 7 days was dominated by cell cycle, signal transduction, metabolism and transport, and transcription genes. Interestingly, the majority of differentially expressed cell cycle genes belonged to the G2 and M phases, suggesting that the proliferating cells were relatively synchronized 1 wk following injury. At 14 days postinjury, the expression profile was similar to that of resting airway epithelium. 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 airway epithelial diseases.

gene expression; lung; repair; cell cycle; microarray




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