PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung
Epithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyro...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/289867 |
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| _version_ | 1832558762305519616 |
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| author | Virender K. Rehan John S. Torday |
| author_facet | Virender K. Rehan John S. Torday |
| author_sort | Virender K. Rehan |
| collection | DOAJ |
| description | Epithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyroid-hormone-related protein, and its binding to its receptor on the mesenchyme, inducing PPARγ expression by lipofibroblasts. Lipofibroblasts then produce leptin, which binds to alveolar type II cells, stimulating their production of surfactant, which is necessary for both evolutionary and physiologic adaptation to atmospheric oxygen from fish to man. A wide variety of molecular insults disrupt such highly evolved physiologic cell-cell interactions, ranging from overdistention to oxidants, infection, and nicotine, all of which predictably cause loss of mesenchymal peroxisome-proliferator-activated receptor gamma (PPARγ) expression and the transdifferentiation of lipofibroblasts to myofibroblasts, the signature cell type for lung fibrosis. By exploiting such deep cell-molecular functional homologies as targets for leveraging lung homeostasis, we have discovered that we can effectively prevent and/or reverse the deleterious effects of these pathogenic agents, demonstrating the utility of evolutionary biology for the prevention and treatment of chronic lung disease. By understanding mechanisms of health and disease as an evolutionary continuum rather than as dissociated processes, we can evolve predictive medicine. |
| format | Article |
| id | doaj-art-ebecf4b24c8241f9b0ebbfb2a12dc129 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-ebecf4b24c8241f9b0ebbfb2a12dc1292025-02-03T01:31:41ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/289867289867PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the LungVirender K. Rehan0John S. Torday1Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California at Los Angeles, Torrance, CA 90502, USADepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California at Los Angeles, Torrance, CA 90502, USAEpithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyroid-hormone-related protein, and its binding to its receptor on the mesenchyme, inducing PPARγ expression by lipofibroblasts. Lipofibroblasts then produce leptin, which binds to alveolar type II cells, stimulating their production of surfactant, which is necessary for both evolutionary and physiologic adaptation to atmospheric oxygen from fish to man. A wide variety of molecular insults disrupt such highly evolved physiologic cell-cell interactions, ranging from overdistention to oxidants, infection, and nicotine, all of which predictably cause loss of mesenchymal peroxisome-proliferator-activated receptor gamma (PPARγ) expression and the transdifferentiation of lipofibroblasts to myofibroblasts, the signature cell type for lung fibrosis. By exploiting such deep cell-molecular functional homologies as targets for leveraging lung homeostasis, we have discovered that we can effectively prevent and/or reverse the deleterious effects of these pathogenic agents, demonstrating the utility of evolutionary biology for the prevention and treatment of chronic lung disease. By understanding mechanisms of health and disease as an evolutionary continuum rather than as dissociated processes, we can evolve predictive medicine.http://dx.doi.org/10.1155/2012/289867 |
| spellingShingle | Virender K. Rehan John S. Torday PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung PPAR Research |
| title | PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung |
| title_full | PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung |
| title_fullStr | PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung |
| title_full_unstemmed | PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung |
| title_short | PPARγ Signaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung |
| title_sort | pparγ signaling mediates the evolution development homeostasis and repair of the lung |
| url | http://dx.doi.org/10.1155/2012/289867 |
| work_keys_str_mv | AT virenderkrehan ppargsignalingmediatestheevolutiondevelopmenthomeostasisandrepairofthelung AT johnstorday ppargsignalingmediatestheevolutiondevelopmenthomeostasisandrepairofthelung |