The angiogenic effects of exosomes secreted from retinal pigment epithelial cells on endothelial cells.
Angiogenesis
Exosome
HUVEC, human umbilical vein endothelial cell
RPE, retinal pigment epithelium
Retinal pigment epithelial cells
TGF-β, transforming growth factor-β
TNF-α, tumour necrosis factor-α
Transforming growth factor
Tumour necrosis factor
Journal
Biochemistry and biophysics reports
ISSN: 2405-5808
Titre abrégé: Biochem Biophys Rep
Pays: Netherlands
ID NLM: 101660999
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
08
11
2019
revised:
17
01
2020
accepted:
11
02
2020
entrez:
19
5
2020
pubmed:
19
5
2020
medline:
19
5
2020
Statut:
epublish
Résumé
Exosomes are informative microvesicles associated with intercellular communication via the transfer of many molecular constituents such as proteins, lipids, and nucleic acids; environmental changes and the cellular status around cells greatly affect exosome components. Cells of the retinal pigment epithelium (RPE) are key players in retinal homeostasis. Transforming growth factor (TGF)-β and tumour necrosis factor (TNF)-α are increased in the vitreous and retina in several retinal diseases and activate and undergo epithelial-mesenchymal transition (EMT) in RPE cells. EMT is closely associated with mechanisms of wound healing, including fibrosis and related angiogenesis; however, whether exosome components depend on the cell status, epithelium or mesenchyme and whether these exosomes have pro- or anti-angiogenic roles in the retina are unknown. We performed this study to investigate whether these EMT inducers affect the kinds of components in exosomes secreted from RPE cells and to assess their angiogenic effects. Exosomes were collected from culture media supernatants of a human RPE cell line (ARPE-19) stimulated with or without 10 ng/ml TNF-α and/or 5 ng/ml TGF-β2. NanoSight tracking analysis and immunoblot analysis using exosome markers were used to qualify harvested vesicles. Angiogenic factor microarray analysis revealed that exosomes derived from ARPE-19 cells cultured with TNF-α alone (Exo-TNF) and co-stimulated with TNF-α and TGF-β2 (Exo-CO) contained more angiogenic factors than exosomes derived from control cells (Exo-CTL) or ARPE-19 cells cultured with TGF-β2 alone (Exo-TGF). To assess the effect on angiogenesis, we performed chemotaxis, tube formation, and proliferation assays of human umbilical vein endothelial cells (HUVECs) stimulated with or without exosomes. HUVECs migrated to RPE-derived exosomes, and exosomes derived from ARPE-19 cells accelerated HUVEC tube formation. In contrast, Exo-TNF and Exo-CO reduced HUVEC proliferation. Our findings provide insight into the mechanisms underlying the relation between angiogenesis and exosomes derived from RPE cells.
Identifiants
pubmed: 32420462
doi: 10.1016/j.bbrep.2020.100760
pii: S2405-5808(20)30069-8
pii: 100760
pmc: PMC7218265
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100760Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
None.
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