Retinal pigment epithelial cells secrete miR-202-5p-containing exosomes to protect against proliferative diabetic retinopathy. (December 2020)

• Record Type: Journal Article
• Authors: Gu, Shun; Liu, Yixiao; Zou, Jian; Wang, Wenjuan; Wei, Tingting; Wang, Xiaolu; Zhu, Lingpeng; Zhang, Mengyuan; Zhu, Jing; Xie, Tianhua; Yao, Yong; Qiu, Liying
• Is Part Of: Experimental eye research. Volume 201(2020)
• Publication Date: 2020-12
• Subjects: Proliferative diabetic retinopathy -- Retinal pigment epithelial cell -- Endothelial cell -- Exosome -- miR-202-5p -- TGFβR2; endothelial-to-mesenchymal transition (EndoMT) -- proliferative diabetic retinopathy (PDR) -- high glucose (HG) -- human umbilical vein endothelial cells (HUVECs) -- diabetic retinopathy (DR) -- retinal pigment epithelial (RPE) -- endothelial cells (ECs) -- alpha-smooth muscle actin (α-SMA) -- fibroblast specific protein-1 (FSP-1) -- monocyte chemoattractant protein-1 (MCP1) -- normal glucose (NG) -- phosphate-buffered saline (PBS) -- transmission electron microscopy (TEM) -- tumor necrosis factor-alpha (TNF-α) -- vascular endothelial growth factor (VEGF) -- transforming growth factor beta (TGF-β); Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108271
• Languages: English
• ISSNs: 0014-4835

Abstract

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. Highlights: ARPE19 cells release exosomes in high glucose condition. Exosomes from high glucose treated ARPE19 cells modulate phenotypes of HUVECs. Exosomal miR-202-5p regulates the TGFβ signaling pathway by targeting TGFβR2.