Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex
| العنوان: | Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex |
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| المؤلفون: | Maciej M. Markiewski, Sasikanth Manne, Bhaumik Patel, Jun-Hung Cho, Magdalena Karbowniczek, Fabrice Roegiers, Jalpa Patel, Santosh Bonala, Elizabeth P. Henske |
| المصدر: | Oncogene. 35:3027-3036 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, Exosomes, Presenilin, Mice, 03 medical and health sciences, Tuberous Sclerosis, Genetics, medicine, Animals, Humans, Progenitor cell, Molecular Biology, Cell Proliferation, Genome, biology, Cell growth, Phenotype, Microvesicles, Cell biology, 030104 developmental biology, medicine.anatomical_structure, biology.protein, TSC1, TSC2, RHEB |
| الوصف: | Functions of extracellular vesicles including exosomes in the pathogenesis of tuberous sclerosis complex (TSC) have not yet been studied. We report that the extracellular vesicles such as exosomes derived from tuberous sclerosis 1 (Tsc1)-null cells transform phenotypes of neighboring wild-type cells in vivo in such manner that they become functionally similar to Tsc1-null cells. The loss of Tsc1 in the mouse neural tube increases the number of the wild-type neuronal progenitors, which is followed by the precocious and transient acceleration of neuronal differentiation of these cells. The mechanisms regulating these changes involve the exosomal delivery of exosomal shuttle Notch1 and Rheb esRNA and component of γ-secretase complex presenilin 1 from Tsc1-null cells to wild-type cells leading to the activation of Notch and Rheb signaling in the recipient cells. The exosome-mediated mechanisms may also operate in the cells of angiomyolipoma (AML), which develops as a result of mutations in TSC1/TSC2 genes in TSC patients, because we observed the reactivation of mammalian target of rapamycin and Notch pathways, driven by the delivery of Rheb and Notch1 esRNA, in AML cells depleted of Rheb that were treated with the exosomes purified from AML cells with the constitutively high Rheb levels. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a8461bb00c71c0243162b442c53d0eeTest https://doi.org/10.1038/onc.2015.358Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9a8461bb00c71c0243162b442c53d0ee |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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