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Transcriptional Networks – Control of Lung Maturation

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Pediatric Biomedical Informatics

Part of the book series: Translational Bioinformatics ((TRBIO,volume 2))

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Abstract

This chapter provides examples of the application of tools of bioinformatics and functional genomics to integration of large-scale gene expression data with array independent genomic information to reveal transcriptional regulatory networks. The focus is on networks that control lung maturation and surfactant homeostasis, which can serve as a prototype for study of other complex biological processes. Prenatal maturation of the respiratory system is fundamentally important for the transition to airbreathing at birth. Lung immaturity is a major cause of morbidity and mortality in newborn infants and underlies the pathogenesis of acute respiratory failure (respiratory distress syndrome) and chronic respiratory dysfunction (bronchopulmonary dysplasia), associated with preterm birth. The immaturity of type II alveolar epithelial cells and the lack of pulmonary surfactant lipids and proteins that are needed to reduce surface tension in the alveolar saccules cause atelectasis and respiratory insufficiency after preterm birth. Lung maturation includes diverse structural, cellular, and biochemical changes in lung architecture and function that are precisely coordinated by genetic and environmental factors that synchronize the length of gestation with the process of lung maturation. Analysis of lung specific gene deletion and mutation mouse models, using tools of functional genomics, permits the identification of new genes and pathways controlling surfactant lipid homeostasis and lung maturation. The signaling and transcriptional mechanisms that influence lung growth and maturation needed to support the abrupt adaptation to airbreathing at birth are of considerable interest, and will provide a rational basis for the design of new treatment strategies for neonatal pulmonary disease.

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Authors and Affiliations

  1. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Yan Xu Ph.D. & Jeffrey A. Whitsett M.D.

  2. Divisions of Pulmonary Biology and Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC7009, Cincinnati, OH, 45229-3039, USA

    Yan Xu Ph.D.

  3. Perinatal Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC7009, Cincinnati, OH, 45229-3039, USA

    Jeffrey A. Whitsett M.D.

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  1. Yan Xu Ph.D.
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Correspondence to Yan Xu Ph.D. .

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  1. Burnet Ave 3333, Cincinnati, 45229-3026, Ohio, USA

    John J. Hutton

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Xu, Y., Whitsett, J.A. (2012). Transcriptional Networks – Control of Lung Maturation. In: Hutton, J. (eds) Pediatric Biomedical Informatics. Translational Bioinformatics, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5149-1_17

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