Li Ziyu, Zheng Meige, Yu Shuisheng, Yao Fei, Luo Yang, Liu Yanchang, Tian Dasheng, Cheng Li, Jing Juehua
Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei, China.
Front Pharmacol. 2021 Apr 15;12:670813. doi: 10.3389/fphar.2021.670813. eCollection 2021.
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.
血小板衍生生长因子受体β阳性（PDGFRβ）周细胞形成纤维化瘢痕，这会阻止脊髓损伤（SCI）后轴突再生。然而，PDGFRβ周细胞迁移至损伤核心的机制尚不清楚。在此，我们研究了巨噬细胞极化对SCI后PDGFRβ周细胞迁移的影响及机制。巨噬细胞与损伤后3、7和14天（dpi）损伤核心中PDGFRβ周细胞的时空分布密切相关。巨噬细胞在3和7 dpi时呈现M2极化，而在14 dpi时呈现M1极化。SCI后以及巨噬细胞M2极化后，血小板衍生生长因子B（PDGFB）的表达显著增加。外源性PDGFB和M2巨噬细胞条件培养基对PDGFRβ周细胞迁移的促进作用可被PDGFRβ特异性抑制剂SU16f阻断。这些发现表明，M2巨噬细胞可分泌PDGFB作用于PDGFRβ，以促进PDGFRβ周细胞迁移，而这一过程可被PDGFRβ特异性抑制剂SU16f阻断。PDGFB/PDGFRβ通路是治疗SCI的一个有前景的新靶点。
