Microvascular patterning is controlled by fine-tuning the Akt signal
| Autor: | Talia Dor, J. Nalinee Upalakalin, Ichiro Shiojima, Thuy L. Phung, Dian Feng, Tad Kornaga, Laura E. Benjamin, Terri Felske, Kenneth Walsh, Jing Fang Sun, Ann M. Dvorak |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Transgene Neovascularization Physiologic Mice Transgenic Protein Serine-Threonine Kinases Biology Neovascularization Mice chemistry.chemical_compound Proto-Oncogene Proteins Edema Internal medicine medicine Animals RNA Messenger Protein kinase B Skin Multidisciplinary Neovascularization Pathologic Retinal Vessels Retinal Biological Sciences Immunohistochemistry Phenotype Embryonic stem cell Cell biology Endocrinology chemistry medicine.symptom Proto-Oncogene Proteins c-akt Homeostasis Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:128-133 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | We investigated the functions of Akt during vascular development and remodeling by using an inducible endothelial cell-specific driver of the dominant-active myrAkt. We found that sustained signaling in response to overexpression of myrAkt led to embryonic lethality, edema, and vascular malformations. In addition to the morphological malformations, the vascular phenotype was consistent with a failure in remodeling, such that the normal patterning and vessel hierarchy was disturbed. Examination of the well studied retinal vasculature during the remodeling phases revealed that transient expression of myrAkt was capable of altering the normal response to oxygen-induced remodeling without causing vascular malformations. These findings suggest that physiological levels of Akt signaling modulated microvascular remodeling and support the hypothesis that, although Akt may be required for vascular growth and homeostasis, appropriate down-regulation is also an essential aspect of normal vascular patterning. |
| Databáze: | OpenAIRE |
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