Funk Lucy H, Hackett Amber R, Bunge Mary Bartlett, Lee Jae K
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL, 33136, USA.
Department of Cell Biology, University of Miami School of Medicine, Miami, FL, 33136, USA.
J Neuroinflammation. 2016 Apr 20;13(1):87. doi: 10.1186/s12974-016-0552-4.
Fibrotic scar formation contributes to the axon growth-inhibitory environment that forms following spinal cord injury (SCI). We recently demonstrated that depletion of hematogenous macrophages led to a reduction in fibrotic scar formation and increased axon growth after SCI. These changes were associated with decreased TNFSF13 (a proliferation inducing ligand (APRIL)) expression, but the role of APRIL in fibrotic scar formation after SCI has not been directly investigated. Thus, the goal of this study was to determine the role of APRIL in fibrotic scar formation after SCI.
APRIL knockout and wild-type mice received contusive SCI and were assessed for inflammatory cytokine/chemokine expression, leukocyte infiltration, fibrotic scar formation, axon growth, and cell proliferation.
Expression of APRIL and its receptor BCMA is increased following SCI, and genetic deletion of APRIL led to reduced fibrotic scar formation and increased axon growth. However, the fibrotic scar reduction in APRIL KO mice was not a result of changes in fibroblast or astrocyte proliferation. Rather, APRIL knockout mice displayed reduced TNFα and CCL2 expression and less macrophage and B cell infiltration at the injury site.
Our data indicate that APRIL contributes to fibrotic scar formation after SCI by mediating the inflammatory response.
纤维化瘢痕形成促成了脊髓损伤（SCI）后形成的轴突生长抑制环境。我们最近证明，清除血源性巨噬细胞可减少SCI后的纤维化瘢痕形成并增加轴突生长。这些变化与TNFSF13（增殖诱导配体（APRIL））表达降低有关，但APRIL在SCI后纤维化瘢痕形成中的作用尚未得到直接研究。因此，本研究的目的是确定APRIL在SCI后纤维化瘢痕形成中的作用。
将APRIL基因敲除小鼠和野生型小鼠进行挫伤性SCI，并评估其炎性细胞因子/趋化因子表达、白细胞浸润、纤维化瘢痕形成、轴突生长和细胞增殖情况。
SCI后APRIL及其受体BCMA的表达增加，APRIL基因缺失导致纤维化瘢痕形成减少且轴突生长增加。然而，APRIL基因敲除小鼠中纤维化瘢痕的减少并非成纤维细胞或星形胶质细胞增殖变化的结果。相反，APRIL基因敲除小鼠在损伤部位的TNFα和CCL2表达降低，巨噬细胞和B细胞浸润减少。
我们的数据表明，APRIL通过介导炎症反应促成SCI后纤维化瘢痕形成。
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