Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombo...
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2021-03-01
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doaj-e939b48e368240338dde7109aa1677582021-03-22T05:49:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.606245606245Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling PathwayLei Liu0Qiongling Zhang1Shunli Xiao2Zhengxiao Sun3Shilan Ding4Ying Chen5Lan Wang6Xiaojie Yin7Fulong Liao8Lin-Hua Jiang9Lin-Hua Jiang10Mei Xue11Yun You12Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaSino-UK Joint Laboratory of Brain Function and Injury, Xinxiang Medical University, Xinxiang, ChinaSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomXiYuan Hosipital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaXueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000–2000 s−1) and pathologically related rates (4,000–6,000 s−1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L−1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.https://www.frontiersin.org/articles/10.3389/fphar.2021.606245/fullxueshuantongshearplatelet aggregationpiezo1 channelCa2+ |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Liu Qiongling Zhang Shunli Xiao Zhengxiao Sun Shilan Ding Ying Chen Lan Wang Xiaojie Yin Fulong Liao Lin-Hua Jiang Lin-Hua Jiang Mei Xue Yun You |
spellingShingle |
Lei Liu Qiongling Zhang Shunli Xiao Zhengxiao Sun Shilan Ding Ying Chen Lan Wang Xiaojie Yin Fulong Liao Lin-Hua Jiang Lin-Hua Jiang Mei Xue Yun You Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway Frontiers in Pharmacology xueshuantong shear platelet aggregation piezo1 channel Ca2+ |
author_facet |
Lei Liu Qiongling Zhang Shunli Xiao Zhengxiao Sun Shilan Ding Ying Chen Lan Wang Xiaojie Yin Fulong Liao Lin-Hua Jiang Lin-Hua Jiang Mei Xue Yun You |
author_sort |
Lei Liu |
title |
Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway |
title_short |
Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway |
title_full |
Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway |
title_fullStr |
Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway |
title_full_unstemmed |
Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway |
title_sort |
inhibition of shear-induced platelet aggregation by xueshuantong via targeting piezo1 channel-mediated ca2+ signaling pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-03-01 |
description |
XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000–2000 s−1) and pathologically related rates (4,000–6,000 s−1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L−1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation. |
topic |
xueshuantong shear platelet aggregation piezo1 channel Ca2+ |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.606245/full |
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