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Published on: March 30, 2018
M2 Macrophages Promote PDGFRβ+ Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway
Ziyu Li1, Meige Zheng1, Shuisheng Yu1
1Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei, China.
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.
Insights
Macrophages polarization influences Platelet-Derived Growth Factor Receptor Beta positive (PDGFRβ+) pericyte migration after spinal cord injury (SCI). M2 macrophages secrete PDGFB, promoting pericyte migration via the PDGFB/PDGFRβ pathway, a potential therapeutic target for SCI.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Platelet-derived growth factor receptor β positive (PDGFRβ+) pericytes contribute to fibrotic scarring, inhibiting axonal regeneration post-spinal cord injury (SCI).
- The precise mechanisms driving PDGFRβ+ pericyte migration to the SCI core remain largely unknown.
Purpose of the Study:
- To investigate the role of macrophage polarization in regulating PDGFRβ+ pericyte migration following SCI.
- To elucidate the molecular pathways involved in this interaction.
Main Methods:
- Analysis of macrophage polarization (M1/M2) and PDGFRβ+ pericyte distribution at different time points post-SCI (3, 7, 14 days).
- Assessment of platelet-derived growth factor B (PDGFB) expression.
- In vitro experiments using exogenous PDGFB and M2 macrophage conditioned medium to evaluate pericyte migration, with and without the PDGFRβ inhibitor SU16f.
Main Results:
- Macrophage distribution correlated spatially and temporally with PDGFRβ+ pericytes in the SCI core.
- M2 macrophage polarization was observed early post-injury (3, 7 dpi), preceding M1 polarization (14 dpi).
- PDGFB expression increased post-SCI and with M2 polarization. PDGFB and M2 conditioned medium promoted pericyte migration, an effect inhibited by SU16f.
Conclusions:
- M2 macrophages secrete PDGFB, which promotes PDGFRβ+ pericyte migration by activating the PDGFB/PDGFRβ pathway.
- Inhibition of the PDGFB/PDGFRβ pathway using SU16f can block this migration.
- The PDGFB/PDGFRβ pathway represents a promising therapeutic target for mitigating scar formation and promoting axonal regeneration after SCI.
