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Transforming Growth Factor-β Peptide Signaling in Pulmonary Development, Bronchopulmonary Dysplasia, Fibrosis, and Emphysema

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Transforming Growth Factor-β in Cancer Therapy, Volume I

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Transforming growth factor-β (TGF-β)1, 2 and 3 peptide superfamily signaling is not only essential for both prenatal and postnatal lung morphogenesis, but also plays a key role in the pathobiology of bronchopulmonary dysplasia, pulmonary fibrosis and emphysema. The respective null mutations of TGF-β1 reveals its function to protect against lung inflammation, of TGF-β2 in cardiopulmonary morphogenesis and of TGF-β3 in lung and palatal fusion. TGF-β signal transduction is tightly regulated at all levels from ligand bioavailability in the extracellular space to the nucleus. Protease-antiprotease balance, correct final assembly of lung matrix and hence completion of alveolarization are all important normal functions of the TGF-β signaling pathway. The consequences of excess TGF-β signaling depend on the developmental stage of the lung: alveolar hypoplasia and fibrosis in the growing lung, fibrosis in the adult lung. While inflammation can induce excessive TGF-β signaling, lung fibrosis per se is inflammation independent and mediated by excessive TGF-β and Smad3 signaling. Therapeutic manipulation of TGF-β-Smad3 function is therefore a rational target. However, its application to pulmonary medicine will not be easy because of the narrow therapeutic range and many-layered physiological regulation of this pathway.

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Authors and Affiliations

  1. Developmental Biology Program, Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    David Warburton Dsc, MD, FRCP, FRCS, Wei Shi MD, PhD & Jack Gauldie PhD

  2. Department of Pathology and Medical Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

    Martin Kolb MD, PhD

Authors
  1. David Warburton Dsc, MD, FRCP, FRCS
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  2. Wei Shi MD, PhD
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  3. Martin Kolb MD, PhD
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  4. Jack Gauldie PhD
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© 2008 Humana Press

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Warburton, D., Shi, W., Kolb, M., Gauldie, J. (2008). Transforming Growth Factor-β Peptide Signaling in Pulmonary Development, Bronchopulmonary Dysplasia, Fibrosis, and Emphysema. In: Transforming Growth Factor-β in Cancer Therapy, Volume I. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-292-2_39

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  • DOI: https://doi.org/10.1007/978-1-59745-292-2_39

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-714-3

  • Online ISBN: 978-1-59745-292-2

  • eBook Packages: MedicineMedicine (R0)

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