M2 Macrophages Promote Pdgfr Beta(+) Pericytes Migration After Spinal Cord Injury In Mice Via Pdgfb/Pdgfr Beta Pathway

FRONTIERS IN PHARMACOLOGY(2021)

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摘要
Platelet derived growth factor receptor beta positive (PDGFR beta(+)) pericytes form fibrotic scar, which prevents axonal regeneration after spinal cord injury (SCI). However, the mechanism by which PDGFR beta(+) pericytes migrate to the injury core is unclear. Here, we investigated the effect and mechanism of macrophages polarization on PDGFR beta(+) pericytes migration after SCI. Macrophages were closely related to the spatiotemporal distribution of PDGFR beta(+) 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 PDGFR beta(+) pericytes migration could be blocked by SU16f, a PDGFR beta specific inhibitor. These findings indicate that M2 macrophages can secrete PDGFB acting on PDGFR beta to promote PDGFR beta(+) pericytes migration, which can be blocked by a PDGFR beta specific inhibitor SU16f. The PDGFB/PDGFR beta pathway is a promising new target for the treatment of SCI.
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关键词
spinal cord injury, M2 macrophages, PDGFR&#946, (+) pericytes, PDGFR&#946, fibrotic scar
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