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Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells.

TitleVasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsOosthuyzen W, Scullion KM, Ivy JR, Morrison EE, Hunter RW, Lewis PJStarkey, O'Duibhir E, Street JM, Caporali A, Gregory CD, Forbes SJ, Webb DJ, Bailey MA, Dear JW
JournalJ Am Soc Nephrol
Date Published2016 Mar 28
ISSN1533-3450
Abstract

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 mCCDC11cells 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 mCCDC11cells 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 ECVsin 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.

DOI10.1681/ASN.2015050568
Alternate JournalJ. Am. Soc. Nephrol.
PubMed ID27020854
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