Bisperoxovanadium induces M2-type macrophages and promotes functional recovery after spinal cord injury
Bisperoxovanadium induces M2-type macrophages and promotes functional recovery after spinal cord injury
复制标题
双过氧钒诱导M2型巨噬细胞并促进脊髓损伤后功能恢复
DOI：
10.1016/j.molimm.2019.09.022
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发表时间：
2019-12-01
影响因子：
3.6
通讯作者：
Tang, Yujin
中科院分区：
文献类型：
--
作者：
Liu, Jia;Li, Kai;Tang, Yujin
巨噬细胞可以朝向经典活化的促炎（Ml）状态极化，或者朝向活化的抗炎（M2）状态极化。Ml细胞被toll样受体（TLR）或干扰素（IFN）-γ的配体激活，并且具有毒性作用，而M2细胞被白细胞介素（IL）-4、IL-10和IL-13激活，并且在体外和体内具有再生作用。以前的研究表明，这些细胞在脊髓损伤（SCI）后的炎症反应中起重要作用。从机制上讲，PTEN在巨噬细胞极化调节中的作用尚未完全阐明。在本研究中，我们首先评估了SCI后巨噬细胞中PTEN的表达。我们发现脊髓损伤后，巨噬细胞中PTEN的表达增加。在RAW264.7细胞中敲低PTEN或用bpV（pic）抑制磷酸化PTEN导致M2极化增加和M1极化减少。在大鼠脊髓损伤模型中，含有bpV（pic）的移植物减少脊髓组织空化并促进运动改善，而bpV（pic）和脱细胞脊髓（ASC）支架组合的移植物显示出更好的效果。此外，含有bpV（pic）的移植物在SCI期间增强了巨噬细胞中的M2极化并降低了M1极化。因此，我们已经确定，PTEN是至关重要的极化的巨噬细胞和SCI的功能恢复。靶向PTEN可促进SCI后巨噬细胞向M2极化，促进功能恢复，提示PTEN可能成为SCI治疗的新靶点。
Macrophages can be polarized towards either a classically activated pro-inflammatory (Ml) state, or alternatively towards an activated anti-inflammatory (M2) state. Ml cells are activated by ligands of toll-like receptor (TLR) or interferon (IFN)-gamma and have a toxic effect, whereas M2 cells are activated by interleukin (IL)-4, IL-10, and IL-13 and have a regenerative effect in vitro and in vivo. Previously studies have shown that these cells play an important role in the inflammatory responses following spinal cord injury (SCI). Mechanistically, the role of PTEN in the regulation of macrophage polarization has yet to be fully elucidated. In the present study, we first evaluated the expression of PTEN in macrophages after SCI. We found that PTEN expression was accumulated in the macrophages after the SCI surgery. Knock-down of PTEN or inhibition of phospho-PTEN with bpV(pic) in RAW264.7 cells resulted in increased M2 polarization and decreased M1 polarization. In a rat model of SCI, grafts containing bpV(pic) reduced spinal tissue cavitation and promoted locomotor improvement, while combining grafts of bpV(pic) and acellular spinal cord (ASC) scaffolds showed a better effect. Moreover, grafts containing bpV(pic) enhanced M2 polarization and decreased M1 polarization in the macrophages during SCI. Thus, we have established that PTEN is critical for the polarization of macrophages and the functional recovery of SCI. Targeting PTEN enhances the macrophages towards to M2 polarization and promoting the functional recovery in SCI, and this suggest that PTEN may be a future therapeutic target for SCI treatment.