Chen Susu, Wang Wenyan, Cao Qilong, Wu Shen, Wang Ningli, Ji Lixia, Zhu Wei
School of Pharmacy, Qingdao University, Qingdao, China.
Department of Clinical Pharmacy, The Second Hospital of Traditional Chinese Medicine of Huangdao District, Qingdao, China.
Front Pharmacol. 2022 Jul 19;13:881286. doi: 10.3389/fphar.2022.881286. eCollection 2022.
The trabecular meshwork (TM) is responsible for intraocular pressure (IOP) homeostasis in the eye. The tissue senses IOP fluctuations and dynamically adapts to the mechanical changes to either increase or decrease aqueous humor outflow. Cationic mechanosensitive channels (CMCs) have been reported to play critical roles in mediating the TM responses to mechanical forces. However, how CMCs influence TM cellular function affect aqueous humor drainage is still elusive. In this study, human TM (HTM) cells were collected from a Chinese donor and subjected to cyclically equiaxial stretching with an amplitude of 20% at 1 Hz GsMTx4, a non-selective inhibitor for CMCs, was added to investigate the proteomic changes induced by CMCs in response to mechanical stretch of HTM. Gene ontology enrichment analysis demonstrated that inhibition of CMCs significantly influenced several biochemical pathways, including store-operated calcium channel activity, microtubule cytoskeleton polarity, toll-like receptor signaling pathway, and neuron cell fate specification. Through heatmap analysis, we grouped 148 differentially expressed proteins (DEPs) into 21 clusters and focused on four specific patterns associated with Ca homeostasis, autophagy, cell cycle, and cell fate. Our results indicated that they might be the critical downstream signals of CMCs adapting to mechanical forces and mediating AH outflow.
小梁网（TM）负责维持眼内的眼压（IOP）稳态。该组织能感知眼压波动，并动态适应机械变化以增加或减少房水流出。据报道，阳离子机械敏感通道（CMC）在介导小梁网对机械力的反应中起关键作用。然而，CMC如何影响小梁网细胞功能进而影响房水引流仍不清楚。在本研究中，从一名中国供体采集人小梁网（HTM）细胞，并在1Hz频率下以20%的幅度进行周期性等轴拉伸，添加CMC的非选择性抑制剂GsMTx4，以研究CMC响应HTM的机械拉伸所诱导的蛋白质组变化。基因本体富集分析表明，抑制CMC会显著影响多个生化途径，包括储存性钙通道活性、微管细胞骨架极性、Toll样受体信号通路和神经元细胞命运特化。通过热图分析，我们将148个差异表达蛋白（DEP）分为21个簇，并聚焦于与钙稳态、自噬、细胞周期和细胞命运相关的四种特定模式。我们的结果表明，它们可能是CMC适应机械力并介导房水流出的关键下游信号。
