Department of Biomedical Engineering, University of North Texas, USA.
North Texas Eye Research Institute, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, USA.
Exp Eye Res. 2021 Mar;204:108445. doi: 10.1016/j.exer.2021.108445. Epub 2021 Jan 16.
Piezo1 (also known as Fam38A) is a mechanosensing channel required for mechanotransduction in various cell types. In astrocytes, Piezo1 activation is associated with the pathogenesis of central nervous system neurodegeneration. Expression of Piezo1 has been detected in mouse optic nerve head astrocytes, however, the functional role of Piezo1 has not been identified. In this study, we investigated the role of Piezo1 in optic nerve head astrocyte reactivity. Primary mouse optic nerve head astrocytes were cultured and subjected to mechanical stretch. The expression level of Piezo1 was determined by quantitative PCR and immunocytochemistry staining. Astrocytes were further treated with Yoda1, a specific Piezo1 agonist. The intracellular calcium concentration and expression of F-actin and fibronectin were determined in Yoda1 treated cells. We found that mechanical stretch activated Piezo1 in optic nerve head astrocytes. Yoda1 induced robust Ca responses in a dose dependent manner. In addition, Yoda1 treated cells showed a redistribution of F-actin cytoskeleton and an increased expression of fibronectin which indicated astrocyte reactivity. Our results suggest that Piezo1 responses to mechanical stimulation and plays a role in astrocyte reactivity. This study provides new insights into optic nerve head astrocyte mechanotransduction.
Piezo1（也称为 Fam38A）是各种细胞类型机械转导所需的机械敏感通道。在星形胶质细胞中，Piezo1 的激活与中枢神经系统神经退行性变的发病机制有关。已经在小鼠视神经头星形胶质细胞中检测到 Piezo1 的表达，但是Piezo1 的功能作用尚未确定。在这项研究中，我们研究了 Piezo1 在视神经头星形胶质细胞反应性中的作用。原代培养的小鼠视神经头星形胶质细胞并进行机械拉伸。通过定量 PCR 和免疫细胞化学染色来确定 Piezo1 的表达水平。用 Yoda1（一种特异性 Piezo1 激动剂）进一步处理星形胶质细胞。在 Yoda1 处理的细胞中测定细胞内钙离子浓度以及 F-肌动蛋白和纤维连接蛋白的表达。我们发现机械拉伸激活了视神经头星形胶质细胞中的 Piezo1。Yoda1 以剂量依赖性方式诱导强烈的 Ca 反应。此外，Yoda1 处理的细胞显示出 F-肌动蛋白细胞骨架的重新分布和纤维连接蛋白表达增加，表明星形胶质细胞反应性。我们的结果表明，Piezo1 对机械刺激做出反应，并在星形胶质细胞反应性中起作用。这项研究为视神经头星形胶质细胞机械转导提供了新的见解。
