Up-Regulation of Receptors for Advanced Glycation End-Products by Alveolar Epithelium Influences Cytodifferentiation and Causes Severe Lung Hypoplasia
| Autor: | Megan P. Stogsdill, Paul R. Reynolds, Jeffrey A. Stogsdill, Nicholas B. Heimann |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Pathology Organogenesis Mesenchyme Alveolar Epithelium Receptor for Advanced Glycation End Products Clinical Biochemistry Respiratory Mucosa Biology Mice Glycation Internal medicine medicine Animals Humans Receptors Immunologic Respiratory system Receptor Molecular Biology Mice Knockout Respiratory Distress Syndrome Newborn Lung Infant Newborn Cell Differentiation Cell Biology respiratory system Antigens Differentiation Epithelium Up-Regulation Pulmonary Alveoli medicine.anatomical_structure Endocrinology Animals Newborn Lung morphogenesis |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 45:1195-1202 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Receptors for advanced glycation end-products (RAGE) are cell-surface receptors expressed by pulmonary tissue that influence alveolar type (AT) II-ATI transition required for normal alveolar formation. However, the precise contribution of RAGE in interactions between pulmonary epithelium and splanchnic mesenchyme during lung organogenesis remains uncertain. To test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that overexpress RAGE. Mice that overexpress RAGE throughout embryogenesis experienced 100% mortality and significant lung hypoplasia coincident with large, vacuous areas in the periphery when compared with normal airway and alveolar architecture observed in control mouse lungs. Flow cytometry and immunohistochemistry employing cell-specific markers for distal (forkhead box protein A2) and respiratory (thyroid transcription factor-1) epithelium, ATII cells (pro-surfactant protein-C), and ATI cells (T1-α) demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation. These results reveal that precise regulation of RAGE expression is required during lung formation. Furthermore, abundant RAGE results in profound alterations in epithelial cell differentiation that culminate in severe respiratory distress and perinatal lethality. |
| Databáze: | OpenAIRE |
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