Our hypothesis is that the surface proteins interact with the phospholipids and participate in the regulation of surfactant homeostasis. The goals of this project are to characterize the normal forms assumed by the lipid and protein components of surfactant from secretion by type II cells to alveolar clearance, recycling and catabolism. Normal radiolabeled lipid and protein components of surfactant will be used to identify the forms taken in the airspace by which component in vivo. Parallel experiments will be used to study how the surfactant components move through the form conversions of surfactant in vitro. The importance to and effects of the surfactant protein components SP-A, SP-B, and SP-C on surfactant form conversions in vitro and surfactant function will be evaluated using transgenic mice that are deficient or have abnormal levels of expression of the surfactant proteins. Surfactant component clearance from the airspaces, and recycling and/or catabolism will be quantified using an analog of dipalmitoylphosphatidylcholine and surfactant proteins with residualizing carbohydrate adducts that are not catabolized. The relative importance of type II cells, Clara cells and macrophages to surfactant homeostasis will be quantified, and subcellular organelles important to surfactant component trafficking will be identified using confocal microscopy. Understanding normal surfactant homeostasis will permit new insights into lung dysfunction with injury.
| Whitsett, Jeffrey A; Weaver, Timothy E (2015) Alveolar development and disease. Am J Respir Cell Mol Biol 53:1-7 |
| Conkright, Juliana J; Apsley, Karen S; Martin, Emily P et al. (2010) Nedd4-2-mediated ubiquitination facilitates processing of surfactant protein-C. Am J Respir Cell Mol Biol 42:181-9 |
| Xu, Yan; Zhang, Minlu; Wang, Yanhua et al. (2010) A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics 11:451 |
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| Whitsett, Jeffrey A; Wert, Susan E; Weaver, Timothy E (2010) Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 61:105-19 |
| Bein, Kiflai; Wesselkamper, Scott C; Liu, Xiangdong et al. (2009) Surfactant-associated protein B is critical to survival in nickel-induced injury in mice. Am J Respir Cell Mol Biol 41:226-36 |
| Kramer, Elizabeth L; Mushaben, Elizabeth M; Pastura, Patricia A et al. (2009) Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol 41:415-25 |
| Wang, Mei; Bridges, James P; Na, Cheng-Lun et al. (2009) Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-associated degradation of surfactant protein C. J Biol Chem 284:33377-83 |
| Hardie, William D; Glasser, Stephan W; Hagood, James S (2009) Emerging concepts in the pathogenesis of lung fibrosis. Am J Pathol 175:3-16 |
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