The purpose of this study was to investigate the role of exosomes derived from platelet-rich plasma (PRP-Exos) in the regulation of the fibrogenic activity of Müller cells and the underlying mechanism. We studied the effects of PRP-Exos on the fibrogenic activity of human retinal Müller cells (hMCs) in vitro. PRP-Exos were isolated from the plasma of diabetic rats (DM-PRP-Exos) and normal control rats (Nor-PRP-Exos) and then observed by transmission electron microscopy. After treatment with DM-PRP-Exos or Nor-PRP-Exos, the proliferation and migration of hMCs were measured in vitro. Western blotting was conducted to assess the levels of fibrogenic molecules and activation of Yes-associated protein (YAP) and the PI3K-Akt signalling pathway. In cultured hMCs, DM-PRP-Exos but not Nor-PRP-Exos effectively increased the proliferative and migratory activities and improved connective tissue growth factor (CTGF) and fibronectin expression. Genetic and pharmacological suppression of YAP could reduce the proliferative and migratory activities of hMCs induced by DM-PRP-Exo. Additionally, YAP knockdown inhibited the DM-PRP-Exo-induced up-regulation of CTGF and fibronectin. Furthermore, DM-PRP-Exo-induced PI3K-Akt signalling mediated YAP activation and the expression of CTGF and fibronectin. In summary, DM-PRP-Exos, through YAP activation, enhance both the proliferation and fibrogenic activity of Müller cells via the PI3K/Akt pathway.

中文翻译：

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源自富含血小板的血浆的外泌体通过PI3K / Akt途径激活YAP并促进Müller细胞的纤维化活性。

这项研究的目的是研究富含血小板血浆（PRP-Exos）衍生的外泌体在调节Müller细胞纤维化活性及其潜在机制中的作用。我们研究了PRP-Exos对人视网膜Müller细胞（hMCs）的纤维化活性的影响。从糖尿病大鼠（DM-PRP-Exos）和正常对照大鼠（Nor-PRP-Exos）的血浆中分离出PRP-Exos，然后通过透射电子显微镜观察。用DM-PRP-Exos或Nor-PRP-Exos处理后，在体外测量了hMC的增殖和迁移。进行了蛋白质印迹，以评估纤维化分子的水平以及Yes相关蛋白（YAP）和PI3K-Akt信号通路的激活。在培养的hMC中，DM-PRP-Exos而非Nor-PRP-Exos有效地增加了增殖和迁移活性，并改善了结缔组织生长因子（CTGF）和纤连蛋白的表达。YAP的遗传和药理抑制作用可能会降低DM-PRP-Exo诱导的hMC的增殖和迁移活性。此外，YAP组合式抑制DM-PRP-Exo诱导的CTGF和纤连蛋白的上调。此外，DM-PRP-Exo诱导的PI3K-Akt信号传导介导YAP激活以及CTGF和纤连蛋白的表达。总之，DM-PRP-Exos通过YAP激活，可通过PI3K / Akt途径增强Müller细胞的增殖和纤维化活性。YAP的遗传和药理抑制作用可能会降低DM-PRP-Exo诱导的hMC的增殖和迁移活性。此外，YAP组合式抑制DM-PRP-Exo诱导的CTGF和纤连蛋白的上调。此外，DM-PRP-Exo诱导的PI3K-Akt信号传导介导YAP激活以及CTGF和纤连蛋白的表达。总之，DM-PRP-Exos通过YAP激活，可通过PI3K / Akt途径增强Müller细胞的增殖和纤维化活性。YAP的遗传和药理抑制作用可能会降低DM-PRP-Exo诱导的hMC的增殖和迁移活性。此外，YAP组合式抑制DM-PRP-Exo诱导的CTGF和纤连蛋白的上调。此外，DM-PRP-Exo诱导的PI3K-Akt信号传导介导YAP激活以及CTGF和纤连蛋白的表达。总之，DM-PRP-Exos通过YAP激活，可通过PI3K / Akt途径增强Müller细胞的增殖和纤维化活性。