TGF-β signaling promotes survival and repair in rat alveolar epithelial type 2 cells during recovery after hyperoxic injury
| Autor: | David Warburton, Wei Shi, Sue Buckley, Lora Barsky |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Cell Survival Pyridines Physiology Cell Culture Techniques Respiratory Mucosa Hyperoxia Biology Rats Sprague-Dawley Tgf β signaling Transforming Growth Factor beta Physiology (medical) In Situ Nick-End Labeling medicine Animals Benzodioxoles OXYGEN EXPOSURE Receptor Inosine medicine.diagnostic_test Cell Cycle Imidazoles Cell Biology Rats Pulmonary Alveoli Fibronectin Bronchoalveolar lavage Cell culture Immunology Cancer research biology.protein Receptors Transforming Growth Factor beta Transforming growth factor medicine.drug |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 294:L739-L748 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Hyperoxic rats treated with inosine during oxygen exposure have increased levels of active transforming growth factor (TGF)-beta in the bronchoalveolar lavage (BAL), yet alveolar epithelial type 2 cells (AEC2) isolated from these animals demonstrate less hyperoxia-induced DNA damage and increased expression of active Smad2. To determine whether TGF-beta1 signaling per se protected AEC2 against hyperoxic damage, freshly isolated AEC2 from hyperoxic rats were incubated with TGF-beta1 for 24 h and assayed for DNA damage by fluorescein-activated cell sorter analysis of TdT-mediated dUTP nick end labeling. TGF-beta1 was protective over a concentration range similar to that in BAL of inosine-treated hyperoxic animals (50-5,000 pg/ml). TGF-beta1 also augmented hyperoxia-induced DNA repair activity and cell migration, stimulated autocrine secretion of fibronectin, accelerated closure of a monolayer scratch wound, and restored hyperoxia-depleted VEGF secretion by AEC2 to normoxic levels. The TGF-beta receptor type I activin-like kinase-4, -5, and -7 inhibitor peptide SB-505124 abolished the protective effect of TGF-beta on hyperoxic DNA damage and increased TdT-mediated dUTP nick end labeling in normoxic cells. These data suggest that endogenous TGF-beta-mediated Smad signaling is required for AEC2 homeostasis in vitro, while exogenous TGF-beta1 treatment of hyperoxia-damaged AEC2 results in a cell that is equipped to survive, repair, migrate, secrete matrix, and induce new blood vessel formation more efficiently than AEC2 primed by hyperoxia alone. |
| Databáze: | OpenAIRE |
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