Abstract |
Previous studies have reported that endothelial-to-mesenchymal transition (EndoMT) contributes to pathological fibrosis in proliferative diabetic retinopathy (PDR). The hypothesis of our study was that exosomes from high glucose (HG)-treated ARPE19 cells reprogram endothelial cell behavior in HG conditions by transferring their genetic contents. Our study showed that ARPE19-derived exosomes were internalized by human umbilical vein endothelial cells (HUVECs). Additionally, miR-202-5p, a miRNA known to target TGFβR2, was enriched in ARPE19-derived exosomes. A dual luciferase reporter assay, qPCR, and western blotting were used to characterize the expression of miR-202-5p and phosphorylation of the TGF/Smad pathway proteins. We showed that miR-202-5p-containing exosomes suppressed HUVEC cell growth, migration, and tube formation. Furthermore, TGFβR2 was confirmed as the target of miR-202-5p. A dual luciferase reporter assay showed that TGFβR2 expression was negatively regulated by miR-202-5p. We also showed that miR-202-5p-containing exosomes suppressed HG-induced EndoMT. These collective results suggested that ARPE-derived exosomes may serve as significant mediators of cell-to-cell crosstalk to suppress EndoMT by transferring miR-202-5p through the TGF/Smad pathway, and may be a potential treatment for PDR patients.
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Authors | Shun Gu, Yixiao Liu, Jian Zou, Wenjuan Wang, Tingting Wei, Xiaolu Wang, Lingpeng Zhu, Mengyuan Zhang, Jing Zhu, Tianhua Xie, Yong Yao, Liying Qiu |
Journal | Experimental eye research
(Exp Eye Res)
Vol. 201
Pg. 108271
(12 2020)
ISSN: 1096-0007 [Electronic] England |
PMID | 33007305
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier Ltd. All rights reserved. |
Chemical References |
- MIRN202 microRNA, human
- MicroRNAs
- RNA
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Topics |
- Apoptosis
- Blotting, Western
- Cells, Cultured
- Diabetic Retinopathy
(genetics, metabolism, pathology)
- Exosomes
(genetics, metabolism, ultrastructure)
- Gene Expression Regulation
- Humans
- MicroRNAs
(biosynthesis, genetics)
- Microscopy, Electron, Transmission
- RNA
(genetics)
- Retinal Pigment Epithelium
(metabolism, pathology)
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