Roger S. Mitchell lecture. Uses of expression microarrays in studies of pulmonary fibrosis, asthma, acute lung injury, and emphysema.
Expression microarrays are a powerful tool that could provide new information about the molecular pathways regulating common lung diseases. To exemplify how this tool can be useful, selected examples of informative experiments are reviewed. In studies relevant to asthma, the cytokine interleukin-13 has been shown to produce many of the phenotypic features of this disease, but the cellular targets in the airways and the molecular pathways activated are largely unknown. We have used microarrays to begin to dissect the different transcriptional responses of primary lung cells to this cytokine. In experiments designed to identify global transcriptional programs responsible for regulating lung inflammation and pulmonary fibrosis, we performed microarray experiments on lung tissue from wild-type mice and mice lacking a member of the integrin family know to be involved in activation of latent transforming growth factor (TGF)-beta. In addition to identifying distinct cluster of genes involved in each of these processes, these studies led to the identification of novel pathways by which TGF-beta can regulate acute lung injury and emphysema. Together, these examples demonstrate how careful application and thorough analysis of expression microarrays can facilitate the discovery of novel molecular targets for intervening in common lung diseases.
Sheppard
Dean
D
Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. deans@itsa.ucsf.edu
D000818:Animals; D000951:Antigens, Neoplasm; D001249:Asthma / Q000235:genetics*; D015870:Gene Expression; D005809:Genes, Regulator; D020022:Genetic Predisposition to Disease; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000235:genetics; D018793:Interleukin-13 / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D053508:Matrix Metalloproteinase 12; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011656:Pulmonary Emphysema / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000235:genetics*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000235:genetics
D000951:Antigens, Neoplasm; D016023:Integrins; D018793:Interleukin-13; D016212:Transforming Growth Factor beta; C073878:integrin alphavbeta6; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12