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

Ziyu Li, Meige Zheng, Shuisheng Yu, Fei Yao, Yang Luo, Yanchang Liu, Dasheng Tian, Li Cheng, Juehua Jing

2021Frontiers in Pharmacology28 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

PDGFBPlatelet-derived growth factor receptorCancer researchCell biologyPericyteMacrophage polarizationSpinal cord injuryMacrophageMedicineChemistryGrowth factorReceptorBiologySpinal cordNeuroscienceInternal medicineEndothelial stem cellIn vitroBiochemistrySpinal Cord Injury ResearchImmune cells in cancerWound Healing and Treatments