Human vascular endothelial cells transport foreign exosomes from cow's milk by endocytosis.
نویسندگان
چکیده
Encapsulation of microRNAs in exosomes confers protection against degradation and a vehicle for shuttling of microRNAs between cells and tissues, and cellular uptake by endocytosis. Exosomes can be found in foods including milk. Humans absorb cow's milk exosomes and deliver the microRNA cargo to peripheral tissues, consistent with gene regulation by dietary nucleic acids across species boundaries. Here, we tested the hypothesis that human vascular endothelial cells transport milk exosomes by endocytosis, constituting a step crucial for the delivery of dietary exosomes and their cargo to peripheral tissues. We tested this hypothesis by using human umbilical vein endothelial cells and fluorophore-labeled exosomes isolated from cow's milk. Exosome uptake followed Michaelis-Menten kinetics (Vmax = 0.057 ± 0.004 ng exosome protein × 40,000 cells/h; Km = 17.97 ± 3.84 μg exosomal protein/200 μl media) and decreased by 80% when the incubation temperature was lowered from 37°C to 4°C. When exosome surface proteins were removed by treatment with proteinase K, or transport was measured in the presence of the carbohydrate competitor d-galactose or measured in the presence of excess unlabeled exosomes, transport rates decreased by 45% to 80% compared with controls. Treatment with an inhibitor of endocytosis, cytochalasin D, caused a 50% decrease in transport. When fluorophore-labeled exosomes were administered retro-orbitally, exosomes accumulated in liver, spleen, and lungs in mice. We conclude that human vascular endothelial cells transport bovine exosomes by endocytosis and propose that this is an important step in the delivery of dietary exosomes and their cargo to peripheral tissues.
منابع مشابه
The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells.
BACKGROUND MicroRNAs play essential roles in gene regulation. A substantial fraction of microRNAs in tissues and body fluids is encapsulated in exosomes, thereby conferring protection against degradation and a pathway for intestinal transport. MicroRNAs in cow milk are bioavailable in humans. OBJECTIVE This research assessed the transport mechanism of bovine milk exosomes, and therefore micro...
متن کاملTransport of Bovine Milk Exosomes by Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal Iec-6 Cells
We have reported that microRNAs (miRNAs, miRs) in bovine milk regulate humangenes. In milk, many miRNAs are encapsulated in exosomes, thereby conferringprotection against degradation and a pathway for intestinal transport of miRNAs. Wehypothesized that the uptake of bovine exosomes in human intestinal colon carcinomaCaco-2 cells and rat primary small intestinal IEC-6 cells is me...
متن کاملChronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes
By virtue of lifestyle change, incidence of type 2 diabetes is increasingly being raised with different up-surging pathologies. This condition found to disqualify endothelial progenitor cells during neo-vascularization. Besides to an aborted differentiation property, malfunctioned paracrine activities exacerbate vascular abnormalities. It is found nano-scaled exosomes play essential roles on re...
متن کاملChronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes
By virtue of lifestyle change, incidence of type 2 diabetes is increasingly being raised with different up-surging pathologies. This condition found to disqualify endothelial progenitor cells during neo-vascularization. Besides to an aborted differentiation property, malfunctioned paracrine activities exacerbate vascular abnormalities. It is found nano-scaled exosomes play essential roles on re...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- American journal of physiology. Cell physiology
دوره 310 10 شماره
صفحات -
تاریخ انتشار 2016