(A) Dynamic light scattering analysis of conditioned medium of
16K PRL–treated HUVECs (50 nM, 24 hours). (B) Flow
cytometry analysis of exosomes purified from HUVEC medium and labeled with
CD63. (C) miR-146a level in exosomes from HUVECs treated with
16K PRL or not treated (NT). (D) Exosome production by HUVECs
treated or not with 16K PRL (50 nM, 48 hours). (E) miR-146a
level in NRCMs treated or not with 16K PRL. (F) Fluorescence
microscopy detecting fusion of miR-146a–loaded endothelial
exosomes labeled with the green fluorescent PHK67 membrane linker with NRCMs
(α-actinin, red; DAPI, blue). Scale bars: 50 μm.
(G) Higher-magnification views of boxed regions in
F. Scale bars: 15 μm. (H) Electron
micrographs of NRCM sections showing vesicles (arrows); after a 16-hour
incubation with HUVEC exosomes, NRCMs showed larger multivesicular vesicles
containing the exosomes (inset; enlarged ×2-fold). Scale bars: 500
nm. (I) miR-146a level in NRCMs exposed to miR-146a-exosomes or
control-exosomes or transfected with pre-miR-146a or pre-miR-control.
(J) Expression level of pri-miR-146a in NRCMs exposed to
miR-146a- or control-exosomes. (K) miR-146a expression level,
(L) metabolic activity, assessed by MTS assay, and
(M) Erbb4 level in NRCMs exposed to
control exosomes, miR-146a exosomes, and miR-146a exosomes cotransfected
with anti-miR-control or anti-miR-146a. All data are mean ± SD
(n ≥ 3). *P < 0.05
vs. respective control; #P < 0.05 vs.
miR-146a-exosomes with anti-miR-control. See also Supplemental Figure 3.