Exosomes mediate an epithelial-mesenchymal transition cascade in retinal pigment epithelial cells: Implications for proliferative vitreoretinopathy.

Exosomes mediate an epithelial-mesenchymal transition cascade in retinal pigment epithelial cells: Implications for proliferative vitreoretinopathy.
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DOI:
10.1111/jcmm.15951
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发表时间:
2020-11
影响因子:
5.3
通讯作者:
Wang F
Wang F
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Y;Wang K;Pan J;Yang S;Yao H;Li M;Li H;Lei H;Jin H;Wang F

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最近,外切体已成为许多生理和病理过程的关键媒介。然而,Exosome在增殖性玻璃体视网膜病变(PVR)中的作用尚未见报道。在本研究中,我们旨在探讨外切体在PVR中的作用。用转化生长因子-β2(TGF-2)诱导视网膜色素上皮(RPE)细胞上皮-间充质转化(EMT),作为PVR的体外模型。从正常RPE细胞和EMTed RPE细胞中提取外切体,并进行鉴定。我们将提取的外切体与受体RPE细胞孵育,并在外切体抑制剂GW4869存在的情况下与EMTed的RPE细胞和受体RPE细胞共同培养。这两个实验都表明,来自EMTed RPE细胞的外切体还有进一步的EMT促进作用。还进行了microRNA测序,以确定两组外切体中的miRNA图谱。我们鉴定了34个差异表达的外体miRNAs(P<0.05)。重要的是,在EMTed的RPE细胞的外切体中发现了miR-543,并且miR-543丰富的外切体显著诱导了受体RPE细胞的EMT。我们的研究表明,外体miRNA在EMT过程中在RPE细胞中差异表达,这些外体miRNAs可能在EMT诱导中发挥关键作用。我们的结果强调了外切体在PVR微环境中作为细胞通信者的重要性。
Exosomes have recently emerged as a pivotal mediator of many physiological and pathological processes. However, the role of exosomes in proliferative vitreoretinopathy (PVR) has not been reported. In this study, we aimed to investigate the role of exosomes in PVR. Transforming growth factor beta 2 (TGFß‐2) was used to induce epithelial‐mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, as an in vitro model of PVR. Exosomes from normal and EMTed RPE cells were extracted and identified. We incubated extracted exosomes with recipient RPE cells, and co‐cultured EMTed RPE cells and recipient RPE cells in the presence of the exosome inhibitor GW4869. Both experiments suggested that there are further EMT‐promoting effects of exosomes from EMTed RPE cells. MicroRNA sequencing was also performed to identify the miRNA profiles in exosomes from both groups. We identified 34 differentially expressed exosomal miRNAs (P <. 05). Importantly, miR‐543 was found in exosomes from EMTed RPE cells, and miR‐543‐enriched exosomes significantly induced the EMT of recipient RPE cells. Our study demonstrates that exosomal miRNA is differentially expressed in RPE cells during EMT and that these exosomal miRNAs may play pivotal roles in EMT induction. Our results highlight the importance of exosomes as cellular communicators within the microenvironment of PVR.
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