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M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway

Platelet derived growth factor receptor β positive (PDGFRβ(+)) pericytes form fibrotic scar, which prevents axonal regeneration after spinal cord injury (SCI). However, the mechanism by which PDGFRβ(+) pericytes migrate to the injury core is unclear. Here, we investigated the effect and mechanism of...

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Autores principales: Li, Ziyu, Zheng, Meige, Yu, Shuisheng, Yao, Fei, Luo, Yang, Liu, Yanchang, Tian, Dasheng, Cheng, Li, Jing, Juehua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082415/
https://www.ncbi.nlm.nih.gov/pubmed/33935795
http://dx.doi.org/10.3389/fphar.2021.670813
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author Li, Ziyu
Zheng, Meige
Yu, Shuisheng
Yao, Fei
Luo, Yang
Liu, Yanchang
Tian, Dasheng
Cheng, Li
Jing, Juehua
author_facet Li, Ziyu
Zheng, Meige
Yu, Shuisheng
Yao, Fei
Luo, Yang
Liu, Yanchang
Tian, Dasheng
Cheng, Li
Jing, Juehua
author_sort Li, Ziyu
collection PubMed
description Platelet derived growth factor receptor β positive (PDGFRβ(+)) pericytes form fibrotic scar, which prevents axonal regeneration after spinal cord injury (SCI). However, the mechanism by which PDGFRβ(+) pericytes migrate to the injury core is unclear. Here, we investigated the effect and mechanism of macrophages polarization on PDGFRβ(+) pericytes migration after SCI. Macrophages were closely related to the spatiotemporal distribution of PDGFRβ(+) pericytes in the injury core at 3, 7, and 14 days postinjury (dpi). Macrophages appeared M2 polarization at 3 and 7 dpi while M1 polarization at 14 dpi. The expression of platelet derived growth factor B (PDGFB) was significantly increased after SCI and after macrophages M2 polarization. The promoting effect of exogenous PDGFB and M2 macrophages conditioned medium on PDGFRβ(+) pericytes migration could be blocked by SU16f, a PDGFRβ specific inhibitor. These findings indicate that M2 macrophages can secrete PDGFB acting on PDGFRβ to promote PDGFRβ(+) pericytes migration, which can be blocked by a PDGFRβ specific inhibitor SU16f. The PDGFB/PDGFRβ pathway is a promising new target for the treatment of SCI.
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spelling pubmed-80824152021-04-30 M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway Li, Ziyu Zheng, Meige Yu, Shuisheng Yao, Fei Luo, Yang Liu, Yanchang Tian, Dasheng Cheng, Li Jing, Juehua Front Pharmacol Pharmacology Platelet derived growth factor receptor β positive (PDGFRβ(+)) pericytes form fibrotic scar, which prevents axonal regeneration after spinal cord injury (SCI). However, the mechanism by which PDGFRβ(+) pericytes migrate to the injury core is unclear. Here, we investigated the effect and mechanism of macrophages polarization on PDGFRβ(+) pericytes migration after SCI. Macrophages were closely related to the spatiotemporal distribution of PDGFRβ(+) pericytes in the injury core at 3, 7, and 14 days postinjury (dpi). Macrophages appeared M2 polarization at 3 and 7 dpi while M1 polarization at 14 dpi. The expression of platelet derived growth factor B (PDGFB) was significantly increased after SCI and after macrophages M2 polarization. The promoting effect of exogenous PDGFB and M2 macrophages conditioned medium on PDGFRβ(+) pericytes migration could be blocked by SU16f, a PDGFRβ specific inhibitor. These findings indicate that M2 macrophages can secrete PDGFB acting on PDGFRβ to promote PDGFRβ(+) pericytes migration, which can be blocked by a PDGFRβ specific inhibitor SU16f. The PDGFB/PDGFRβ pathway is a promising new target for the treatment of SCI. Frontiers Media S.A. 2021-04-15 /pmc/articles/PMC8082415/ /pubmed/33935795 http://dx.doi.org/10.3389/fphar.2021.670813 Text en Copyright © 2021 Li, Zheng, Yu, Yao, Luo, Liu, Tian, Cheng and Jing. 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 Pharmacology
Li, Ziyu
Zheng, Meige
Yu, Shuisheng
Yao, Fei
Luo, Yang
Liu, Yanchang
Tian, Dasheng
Cheng, Li
Jing, Juehua
M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
title M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
title_full M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
title_fullStr M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
title_full_unstemmed M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
title_short M2 Macrophages Promote PDGFRβ(+) Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
title_sort m2 macrophages promote pdgfrβ(+) pericytes migration after spinal cord injury in mice via pdgfb/pdgfrβ pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082415/
https://www.ncbi.nlm.nih.gov/pubmed/33935795
http://dx.doi.org/10.3389/fphar.2021.670813
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