Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin, 300020, China.
Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin, 300020, China.
Exp Eye Res. 2020 Apr;193:107973. doi: 10.1016/j.exer.2020.107973. Epub 2020 Feb 12.
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.
本研究旨在探讨富血小板血浆衍生的外泌体（PRP-Exos）在调节 Müller 细胞纤维生成活性中的作用及其机制。我们研究了 PRP-Exos 在体外对人视网膜 Müller 细胞（hMCs）纤维生成活性的影响。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 hMCs 的增殖和迁移。Western blot 用于评估纤维生成分子的水平以及 Yes 相关蛋白（YAP）和 PI3K-Akt 信号通路的激活。在培养的 hMCs 中，DM-PRP-Exos 而非 Nor-PRP-Exos 可有效增加增殖和迁移活性，并改善结缔组织生长因子（CTGF）和纤连蛋白的表达。YAP 的遗传和药理学抑制可降低 DM-PRP-Exo 诱导的 hMCs 的增殖和迁移活性。此外，YAP 敲低抑制了 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 信号通路介导 YAP 激活以及 CTGF 和纤连蛋白的表达。总之，DM-PRP-Exos 通过 YAP 激活，通过 PI3K/Akt 通路增强 Müller 细胞的增殖和纤维生成活性。
