Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries
Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molec...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933524000906 |
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| author | Javier Abello Ying Yin Yonghui Zhao Josh Maurer Jihui Lee Cherokee Bodell Jahmiera Richee Abigail J. Clevenger Zarek Burton Megan E. Goeckel Michelle Lin Stephanie Grainger Carmen M. Halabi Shreya A. Raghavan Rajan Sah Amber N. Stratman |
| author_facet | Javier Abello Ying Yin Yonghui Zhao Josh Maurer Jihui Lee Cherokee Bodell Jahmiera Richee Abigail J. Clevenger Zarek Burton Megan E. Goeckel Michelle Lin Stephanie Grainger Carmen M. Halabi Shreya A. Raghavan Rajan Sah Amber N. Stratman |
| author_sort | Javier Abello |
| collection | DOAJ |
| description | Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating klf2a, a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed klf2a and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased klf2a levels and decreased vSMC association with arteries. We supported the small molecule findings with in vivo genetic suppression of piezo1 and 2 in zebrafish, resulting in loss of transgelin+ vSMCs on the dorsal aorta. Further, endothelial cell (EC)-specific Piezo1 knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. To determine the underlying mechanism, we used in vitro modeling assays to demonstrate that differential sensing of pulsatile versus laminar flow forces across endothelial cells changes the expression of mural cell differentiation genes. Together, our findings suggest a crucial role for EC Piezo1 in sensing force within large arteries to mediate mural cell differentiation and stabilization of the arterial vasculature. |
| format | Article |
| id | doaj-art-fd053a9e18f0405d9ba02a18725cefc2 |
| institution | Kabale University |
| issn | 0171-9335 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj-art-fd053a9e18f0405d9ba02a18725cefc22025-01-23T05:26:15ZengElsevierEuropean Journal of Cell Biology0171-93352025-03-011041151473Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteriesJavier Abello0Ying Yin1Yonghui Zhao2Josh Maurer3Jihui Lee4Cherokee Bodell5Jahmiera Richee6Abigail J. Clevenger7Zarek Burton8Megan E. Goeckel9Michelle Lin10Stephanie Grainger11Carmen M. Halabi12Shreya A. Raghavan13Rajan Sah14Amber N. Stratman15Department of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USADepartment of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Biomedical Engineering, Texas A&M University, College Station, TX, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO, USADepartment of Cell Biology, Van Andel Research Institute, Grand Rapids, MI, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO, USADepartment of Biomedical Engineering, Texas A&M University, College Station, TX, USADepartment of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA; Center for Cardiovascular Research, Washington University, St Louis, MO, USADepartment of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Correspondence to: Department of Cell Biology and Physiology Washington University School of Medicine, St. Louis, MO 63110, USA.Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating klf2a, a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed klf2a and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased klf2a levels and decreased vSMC association with arteries. We supported the small molecule findings with in vivo genetic suppression of piezo1 and 2 in zebrafish, resulting in loss of transgelin+ vSMCs on the dorsal aorta. Further, endothelial cell (EC)-specific Piezo1 knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. To determine the underlying mechanism, we used in vitro modeling assays to demonstrate that differential sensing of pulsatile versus laminar flow forces across endothelial cells changes the expression of mural cell differentiation genes. Together, our findings suggest a crucial role for EC Piezo1 in sensing force within large arteries to mediate mural cell differentiation and stabilization of the arterial vasculature.http://www.sciencedirect.com/science/article/pii/S0171933524000906Vascular smooth muscleMural cellZebrafishPiezo1Arterial stabilization |
| spellingShingle | Javier Abello Ying Yin Yonghui Zhao Josh Maurer Jihui Lee Cherokee Bodell Jahmiera Richee Abigail J. Clevenger Zarek Burton Megan E. Goeckel Michelle Lin Stephanie Grainger Carmen M. Halabi Shreya A. Raghavan Rajan Sah Amber N. Stratman Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries European Journal of Cell Biology Vascular smooth muscle Mural cell Zebrafish Piezo1 Arterial stabilization |
| title | Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries |
| title_full | Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries |
| title_fullStr | Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries |
| title_full_unstemmed | Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries |
| title_short | Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries |
| title_sort | endothelial cell piezo1 promotes vascular smooth muscle cell differentiation on large arteries |
| topic | Vascular smooth muscle Mural cell Zebrafish Piezo1 Arterial stabilization |
| url | http://www.sciencedirect.com/science/article/pii/S0171933524000906 |
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