Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4
Abstract Aims Neointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying...
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BMC
2021-07-01
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Series: | Stem Cell Research & Therapy |
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Online Access: | https://doi.org/10.1186/s13287-021-02466-8 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yan Wu Yuan-jin Li Liu-liu Shi Yun Liu Yan Wang Xin Bao Wei Xu Lu-yuan Yao Magdaleena Naemi Mbadhi Long Chen Shan Li Xing-yuan Li Zhi-feng Zhang Sen Zhao Ruo-nan Zhang Shi-You Chen Jing-xuan Zhang Jun-mingTang |
spellingShingle |
Yan Wu Yuan-jin Li Liu-liu Shi Yun Liu Yan Wang Xin Bao Wei Xu Lu-yuan Yao Magdaleena Naemi Mbadhi Long Chen Shan Li Xing-yuan Li Zhi-feng Zhang Sen Zhao Ruo-nan Zhang Shi-You Chen Jing-xuan Zhang Jun-mingTang Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4 Stem Cell Research & Therapy Meox1 Sca-1 Neointima SDF-1α CDC42 |
author_facet |
Yan Wu Yuan-jin Li Liu-liu Shi Yun Liu Yan Wang Xin Bao Wei Xu Lu-yuan Yao Magdaleena Naemi Mbadhi Long Chen Shan Li Xing-yuan Li Zhi-feng Zhang Sen Zhao Ruo-nan Zhang Shi-You Chen Jing-xuan Zhang Jun-mingTang |
author_sort |
Yan Wu |
title |
Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4 |
title_short |
Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4 |
title_full |
Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4 |
title_fullStr |
Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4 |
title_full_unstemmed |
Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4 |
title_sort |
spatio-temporal model of meox1 expression control involvement of sca-1-positive stem cells in neointima formation through the synergistic effect of rho/cdc42 and sdf-1α/cxcr4 |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2021-07-01 |
description |
Abstract Aims Neointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying mechanisms during vascular injury are still unknown. Methods and results Aneointimal formation rat model was prepared by carotid artery injury using 2F-Forgaty. After vascular injury, Meox1 expressions time-dependently increased during the neointima formation, with its levels concurrently increasing in the adventitia, media, and neointima. Meox1 was highly expressed in the adventitia on the first day after vascular injury compared to the expression levels in the media. Conversely, by the 14th day post-injury, Meox1 was extensively expressed more in the media and neointima than the adventitia. Analogous to the change of Meox1 in injured artery, Sca-1+ progenitor cells increased in the adventitia wall in a time-dependent manner and reached peak levels on the 7th day after injury. More importantly, this effect was abolished by Meox1 knockdown with shRNA. The enhanced expression of SDF-1α after vascular injury was associated with the markedly enhanced expression levels of Sca1+ progenitor cell, and these levels were relatively synchronously increased within neointima by the 7th day after vascular injury. These special effects were abolished by the knockdown of Meox1 with shRNA and inhibition of CXCR4 by its inhibitor, AMD3100. Finally, Meox1 concurrently regulated SDF-1α expressions in VSMC via activating CDC42, and CDC42 inhibition abolished these effects by its inhibitor, ZCL278. Also, Meox1 was involved in activation of the CXCR4 expression of Sca-1+ progenitor cells by CDC42. Conclusions Spatio-temporal model of Meox1 expression regulates theSca-1+progenitor cell migration during the formation of the neointima through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4. |
topic |
Meox1 Sca-1 Neointima SDF-1α CDC42 |
url |
https://doi.org/10.1186/s13287-021-02466-8 |
work_keys_str_mv |
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doaj-28fcbab50d0a4a6fa65bece8081eac912021-07-11T11:07:14ZengBMCStem Cell Research & Therapy1757-65122021-07-0112111510.1186/s13287-021-02466-8Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4Yan Wu0Yuan-jin Li1Liu-liu Shi2Yun Liu3Yan Wang4Xin Bao5Wei Xu6Lu-yuan Yao7Magdaleena Naemi Mbadhi8Long Chen9Shan Li10Xing-yuan Li11Zhi-feng Zhang12Sen Zhao13Ruo-nan Zhang14Shi-You Chen15Jing-xuan Zhang16Jun-mingTang17Department of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineHebei Medical UniversityDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineCental Lab, Guoyao-Dongfeng Hospital, Hubei University of MedicineDepartment of Biochemistry, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineThe Department of Surgery, University of MissouriDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineDepartment of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of MedicineAbstract Aims Neointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying mechanisms during vascular injury are still unknown. Methods and results Aneointimal formation rat model was prepared by carotid artery injury using 2F-Forgaty. After vascular injury, Meox1 expressions time-dependently increased during the neointima formation, with its levels concurrently increasing in the adventitia, media, and neointima. Meox1 was highly expressed in the adventitia on the first day after vascular injury compared to the expression levels in the media. Conversely, by the 14th day post-injury, Meox1 was extensively expressed more in the media and neointima than the adventitia. Analogous to the change of Meox1 in injured artery, Sca-1+ progenitor cells increased in the adventitia wall in a time-dependent manner and reached peak levels on the 7th day after injury. More importantly, this effect was abolished by Meox1 knockdown with shRNA. The enhanced expression of SDF-1α after vascular injury was associated with the markedly enhanced expression levels of Sca1+ progenitor cell, and these levels were relatively synchronously increased within neointima by the 7th day after vascular injury. These special effects were abolished by the knockdown of Meox1 with shRNA and inhibition of CXCR4 by its inhibitor, AMD3100. Finally, Meox1 concurrently regulated SDF-1α expressions in VSMC via activating CDC42, and CDC42 inhibition abolished these effects by its inhibitor, ZCL278. Also, Meox1 was involved in activation of the CXCR4 expression of Sca-1+ progenitor cells by CDC42. Conclusions Spatio-temporal model of Meox1 expression regulates theSca-1+progenitor cell migration during the formation of the neointima through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.https://doi.org/10.1186/s13287-021-02466-8Meox1Sca-1NeointimaSDF-1αCDC42 |