Department of Orthopaedics, Yancheng City No.1 People's Hospital, China.
Department of Orthopaedics, Yancheng City No.1 People's Hospital, China.
Neuropeptides. 2017 Dec;66:36-44. doi: 10.1016/j.npep.2017.08.002. Epub 2017 Aug 18.
Forkhead box A1 (FOXA1) is a member of the FOX family of transcription factors and involved in various mammalian processes. However, the expression and function of FOXA1 in central nervous system (CNS) are still with limited acquaintance. In present study, we performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of FOXA1 expression in spinal cord. We found that FOXA1 protein levels were significantly increased after SCI and we observed that the expression of FOXA1 is enhanced in the white matter. Meanwhile, double immunofluorescence staining showed that increased levels of FOXA1 were striking in astrocytes and microglia. We also examined the expression of proliferating cell nuclear antigen (PCNA), whose changes were correlated with the expression profiles of FOXA1. In vitro, FOXA1 depletion by siRNA inhibited astrocyte proliferation and migration. Meanwhile, FOXA1 knockdown also reduce cell cycle related proteins. Which indicated that FOXA1 might modulate cell cycle progression and play a crucial role in cell proliferation. Furthermore, FOXA1 knockdown also inhibited LPS-induced synthesis/secretion of IL-1β and TNF-α in primary microglia. These results indicated that FOXA1 might play an important role in pathophysiology after SCI.
叉头框蛋白 A1（FOXA1）是转录因子 FOX 家族的成员，参与多种哺乳动物过程。然而，FOXA1 在中枢神经系统（CNS）中的表达和功能仍知之甚少。在本研究中，我们在成年大鼠中建立了急性脊髓损伤（SCI）模型，研究了脊髓中 FOXA1 表达的动态变化。我们发现 SCI 后 FOXA1 蛋白水平显著增加，并且我们观察到 FOXA1 的表达在白质中增强。同时，双免疫荧光染色显示，星形胶质细胞和小胶质细胞中 FOXA1 的水平显著增加。我们还检查了增殖细胞核抗原（PCNA）的表达，其变化与 FOXA1 的表达谱相关。在体外，通过 siRNA 敲低 FOXA1 抑制了星形胶质细胞的增殖和迁移。同时，FOXA1 敲低也降低了细胞周期相关蛋白的水平。这表明 FOXA1 可能调节细胞周期进程并在细胞增殖中发挥关键作用。此外，FOXA1 敲低还抑制了原代小胶质细胞中 LPS 诱导的 IL-1β 和 TNF-α 的合成/分泌。这些结果表明 FOXA1 可能在 SCI 后的病理生理学中发挥重要作用。
