Platelet-derived growth factor-A and sonic hedgehog signaling direct lung fibroblast precursors during alveolar septal formation
| Autor: | Diann M. McCoy, Stephen E. McGowan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
rac1 GTP-Binding Protein
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Receptor Platelet-Derived Growth Factor alpha Physiology Population Antigens CD34 Mice Transgenic Biology Cell Line Alveolar cells Mice Cell Movement Physiology (medical) Precursor cell Pulmonary fibrosis medicine Animals Antigens Ly Hedgehog Proteins Sonic hedgehog education Lung Cell Proliferation Platelet-Derived Growth Factor education.field_of_study Neuropeptides Membrane Proteins Cell Biology Fibroblasts respiratory system medicine.disease Actins Hedgehog signaling pathway Cell biology Pulmonary Alveoli Ki-67 Antigen medicine.anatomical_structure biology.protein Stem cell Signal Transduction |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 305:L229-L239 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00011.2013 |
| Popis: | Alveolar septal formation is required to support the respiration of growing mammals; in humans effacement of the alveolar surface and impaired gas exchange are critical features of emphysema and pulmonary fibrosis. Platelet-derived growth factor-A (PDGF-A) and its receptor PDGF-receptor-α (PDGFRα) are required for secondary septal elongation in mice during postnatal days 4 through 12 and they regulate the proliferation and septal location of interstitial fibroblasts. We examined lung fibroblasts (LF) to learn whether PDGFRα expression distinguished a population of precursor cells, with enhanced proliferative and migratory capabilities. We identified a subpopulation of LF that expresses sonic hedgehog (Shh) and stem cell antigen-1 (Sca1). PDGF-A and Shh both increased cytokinesis and chemotaxis in vitro, but through different mechanisms. In primary LF cultures, Shh signaled exclusively through a noncanonical pathway involving generation of Rac1-GTP, whereas both the canonical and noncanonical pathways were used by the Mlg neonatal mouse LF cell line. LF preferentially oriented their primary cilia toward their anterior pole during migration. Furthermore, a larger proportion of PDGFRα-expressing LF, which are more abundant at the septal tips, bore primary cilia compared with other alveolar cells. In pulmonary emphysema, destroyed alveolar septa do not regenerate, in part because cells fail to assume a configuration that allows efficient gas exchange. Better understanding how LF are positioned during alveolar development could identify signaling pathways, which promote alveolar septal regeneration. |
| Databáze: | OpenAIRE |
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