Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells
| العنوان: | Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells |
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| المؤلفون: | Jessica R. Ivy, Christopher D. Gregory, David J. Webb, Andrea Caporali, Stuart J. Forbes, Wilna Oosthuyzen, Matthew A. Bailey, Philip J. Starkey Lewis, Eoghan O'Duibhir, Emma E. Morrison, James W. Dear, Jonathan M. Street, Kathleen M. Scullion, Robert W. Hunter |
| المصدر: | Oosthuyzen, W, Scullion, K M, Ivy, J R, Morrison, E E, Hunter, R W, Starkey Lewis, P J, O'Duibhir, E, Street, J M, Caporali, A, Gregory, C D, Forbes, S J, Webb, D J, Bailey, M A & Dear, J W 2016, ' Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells ', Journal of the American Society of Nephrology, vol. 27, no. 11, pp. 3345-3355 . https://doi.org/10.1681/ASN.2015050568 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Vasopressin, medicine.medical_specialty, Adolescent, Vasopressins, medicine.drug_class, Cell Communication, Nephron, Pharmacology, Biology, Kidney, Extracellular Vesicles, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, Internal medicine, medicine, Animals, Humans, Deamino Arginine Vasopressin, Kidney Tubules, Collecting, Cells, Cultured, General Medicine, Extracellular vesicle, medicine.disease, Rats, Basic Research, Intercellular Junctions, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Nephrology, Cell culture, 030220 oncology & carcinogenesis, Diabetes insipidus, Vasopressin Analogue |
| الوصف: | Extracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCDC11 cells required cAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo. We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease. |
| وصف الملف: | application/pdf |
| تدمد: | 1533-3450 1046-6673 |
| DOI: | 10.1681/asn.2015050568 |
| DOI: | 10.1681/ASN.2015050568 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31a2908713ee35abcf4a015f74bb5143 https://doi.org/10.1681/asn.2015050568 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31a2908713ee35abcf4a015f74bb5143 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15333450 10466673 |
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| DOI: | 10.1681/asn.2015050568 |