Abstract
Exosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary nanoparticles similar to mammalian exosomes have attracted attention for these features. In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules (proteins, lipids, and nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated the cellular uptake of blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) and the ability of B-ELNs to modulate the expression of inflammatory genes as the response of tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize B-ELNs in a dose-dependent manner; 2) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species (ROS) generation and loss of cell viability and modulates the differential expression of 29 genes (fold change > 1.5) induced by TNF-α compared to control; 3) pathway analysis reveals their involvement in a total of 340 canonical pathways, 121 KEGG pathways, and 121 GO Biological processes; and 4) the intersection between differentially expressed (DE) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes, such as prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), and phosphodiesterase 7A (PDE7A), for ELNs-contained cargo. In conclusion, our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors.
Highlights
Cell-to-cell communication is a physiological mechanism that contributes in maintaining tissue functions and homeostasis
In Dynamic light scattering (DLS) analysis, the size distribution is weighted by the intensity of scattering, which overestimates the contribution of highest diameters, implying that a few large vesicles can have the same intensity of many small vesicles
We searched for candidate mRNA targets belonging to the panel of DE genes that we found regulated by B-exosome-like nanoparticles (ELNs) (Figure 6) and the genes involved in the pathways most significantly related to inflammatory response, cytokine release and oxidative stress (Figure 7 and Supplementary Table S2)
Summary
Cell-to-cell communication is a physiological mechanism that contributes in maintaining tissue functions and homeostasis. Supporting data coming from independent laboratory indicate that nanoparticles derived from edible plants such as grape and grapefruit [5,11], ginger [12], and carrots [13] have anti-inflammatory properties [14]; ELNs from ginger inhibits inflammasome activation [12]; citrus-lemon ELNs demonstrate anti-oxidant properties and antitumor effect [15,16,17]; and apple-derived nanoparticles could affect intestinal transporters [18]. All these findings open up a new perspectives on the therapeutic potential of natural/food compounds [14,19,20]
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