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Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling
Phenotypic switch of vascular smooth muscle cells (VSMCs) is important in vascular remodeling which causes hyperplasia and restenosis after intimal injury. Platelets are activated at injured intima and secrete platelet-derived microvesicles (PMVs). Herein, we demonstrated the role of PMVs in VSMC ph...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481604/ https://www.ncbi.nlm.nih.gov/pubmed/34604241 http://dx.doi.org/10.3389/fcell.2021.744320 |
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author | Liu, Ji-Ting Bao, Han Fan, Yang-Jing Li, Zi-Tong Yao, Qing-Ping Han, Yue Zhang, Ming-Liang Jiang, Zong-Lai Qi, Ying-Xin |
author_facet | Liu, Ji-Ting Bao, Han Fan, Yang-Jing Li, Zi-Tong Yao, Qing-Ping Han, Yue Zhang, Ming-Liang Jiang, Zong-Lai Qi, Ying-Xin |
author_sort | Liu, Ji-Ting |
collection | PubMed |
description | Phenotypic switch of vascular smooth muscle cells (VSMCs) is important in vascular remodeling which causes hyperplasia and restenosis after intimal injury. Platelets are activated at injured intima and secrete platelet-derived microvesicles (PMVs). Herein, we demonstrated the role of PMVs in VSMC phenotypic switch and the potential underlying mechanisms. In vivo, platelets were locally adhered and activated at intimal injury site, while Lamtor1 was promoted and VSMCs were dedifferentiated. PMVs, collected from collagen-activated platelets in vitro which mimicked collagen exposure during intimal injury, promoted VSMC dedifferentiation, induced Lamtor1 expression, and activated mTORC1 signaling, reflected by the phosphorylation of two downstream targets, i.e., S6K and 4E-BP1. Knockdown of Lamtor1 with small interfering RNA attenuated these processes induced by PMVs. Based on the previously published proteomic data, Ingenuity Pathway Analysis revealed that Src may participate in regulating effects of PMVs. Src inhibitor significantly reversed the effects of PMVs on VSMC dedifferentiation, Lamtor1 expression and mTORC1 activation. Furthermore, in SMC-specific Lamtor1 knockout mice, intimal hyperplasia was markedly attenuated after intimal injury compared with the wild type. Our data suggested that PMVs secreted by activated platelets promoted VSMC dedifferentiation via Src/Lamtor1/mTORC1 signaling pathway. Lamtor1 may be a potential therapeutic target for intimal hyperplasia after injury. |
format | Online Article Text |
id | pubmed-8481604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84816042021-10-01 Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling Liu, Ji-Ting Bao, Han Fan, Yang-Jing Li, Zi-Tong Yao, Qing-Ping Han, Yue Zhang, Ming-Liang Jiang, Zong-Lai Qi, Ying-Xin Front Cell Dev Biol Cell and Developmental Biology Phenotypic switch of vascular smooth muscle cells (VSMCs) is important in vascular remodeling which causes hyperplasia and restenosis after intimal injury. Platelets are activated at injured intima and secrete platelet-derived microvesicles (PMVs). Herein, we demonstrated the role of PMVs in VSMC phenotypic switch and the potential underlying mechanisms. In vivo, platelets were locally adhered and activated at intimal injury site, while Lamtor1 was promoted and VSMCs were dedifferentiated. PMVs, collected from collagen-activated platelets in vitro which mimicked collagen exposure during intimal injury, promoted VSMC dedifferentiation, induced Lamtor1 expression, and activated mTORC1 signaling, reflected by the phosphorylation of two downstream targets, i.e., S6K and 4E-BP1. Knockdown of Lamtor1 with small interfering RNA attenuated these processes induced by PMVs. Based on the previously published proteomic data, Ingenuity Pathway Analysis revealed that Src may participate in regulating effects of PMVs. Src inhibitor significantly reversed the effects of PMVs on VSMC dedifferentiation, Lamtor1 expression and mTORC1 activation. Furthermore, in SMC-specific Lamtor1 knockout mice, intimal hyperplasia was markedly attenuated after intimal injury compared with the wild type. Our data suggested that PMVs secreted by activated platelets promoted VSMC dedifferentiation via Src/Lamtor1/mTORC1 signaling pathway. Lamtor1 may be a potential therapeutic target for intimal hyperplasia after injury. Frontiers Media S.A. 2021-09-16 /pmc/articles/PMC8481604/ /pubmed/34604241 http://dx.doi.org/10.3389/fcell.2021.744320 Text en Copyright © 2021 Liu, Bao, Fan, Li, Yao, Han, Zhang, Jiang and Qi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Liu, Ji-Ting Bao, Han Fan, Yang-Jing Li, Zi-Tong Yao, Qing-Ping Han, Yue Zhang, Ming-Liang Jiang, Zong-Lai Qi, Ying-Xin Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling |
title | Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling |
title_full | Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling |
title_fullStr | Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling |
title_full_unstemmed | Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling |
title_short | Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling |
title_sort | platelet-derived microvesicles promote vsmc dedifferentiation after intimal injury via src/lamtor1/mtorc1 signaling |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481604/ https://www.ncbi.nlm.nih.gov/pubmed/34604241 http://dx.doi.org/10.3389/fcell.2021.744320 |
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