Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch
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...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.881286/full |
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| author | Susu Chen Wenyan Wang Qilong Cao Shen Wu Ningli Wang Lixia Ji Wei Zhu Wei Zhu |
| author_facet | Susu Chen Wenyan Wang Qilong Cao Shen Wu Ningli Wang Lixia Ji Wei Zhu Wei Zhu |
| author_sort | Susu Chen |
| collection | DOAJ |
| description | 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 Ca2+ 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. |
| first_indexed | 2024-12-12T01:14:36Z |
| format | Article |
| id | doaj.art-5df622f1b25a4a8ca3de16bca7e343fb |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T01:14:36Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5df622f1b25a4a8ca3de16bca7e343fb2022-12-22T00:43:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.881286881286Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical StretchSusu Chen0Wenyan Wang1Qilong Cao2Shen Wu3Ningli Wang4Lixia Ji5Wei Zhu6Wei Zhu7School of Pharmacy, Qingdao University, Qingdao, ChinaDepartment of Clinical Pharmacy, The Second Hospital of Traditional Chinese Medicine of Huangdao District, Qingdao, ChinaQingdao Haier Biotech Co.,Ltd., Qingdao, ChinaBeijing Institute of Ophthalmology, Beijing Tongren Hospital Eye Center, Capital Medical University, Beijing, ChinaBeijing Institute of Ophthalmology, Beijing Tongren Hospital Eye Center, Capital Medical University, Beijing, ChinaSchool of Pharmacy, Qingdao University, Qingdao, ChinaSchool of Pharmacy, Qingdao University, Qingdao, ChinaBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University and Capital Medical University, Beijing, ChinaThe 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 Ca2+ 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.881286/fulltrabecular meshworkcationic mechanosensitive channelsmechanical stretchingproteomics analysisIOP homeostasis |
| spellingShingle | Susu Chen Wenyan Wang Qilong Cao Shen Wu Ningli Wang Lixia Ji Wei Zhu Wei Zhu Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch Frontiers in Pharmacology trabecular meshwork cationic mechanosensitive channels mechanical stretching proteomics analysis IOP homeostasis |
| title | Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch |
| title_full | Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch |
| title_fullStr | Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch |
| title_full_unstemmed | Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch |
| title_short | Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch |
| title_sort | cationic mechanosensitive channels mediate trabecular meshwork responses to cyclic mechanical stretch |
| topic | trabecular meshwork cationic mechanosensitive channels mechanical stretching proteomics analysis IOP homeostasis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.881286/full |
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