Wang Jianhao, Deng Xiangyi, Xie Yuan, Tang Jiefu, Zhou Ziwei, Yang Fan, He Qiyuan, Cao Qingze, Zhang Lei, He Liqun
Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Ministry of Education and Tianjin City, Tianjin, China.
Key Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, China.
Front Genet. 2021 Jan 11;11:599834. doi: 10.3389/fgene.2020.599834. eCollection 2020.
Vasculature plays critical roles in the pathogenesis and neurological repair of traumatic brain injury (TBI). However, how vascular endothelial cells respond to TBI at the molecular level has not been systematically reviewed. Here, by integrating three transcriptome datasets including whole cortex of mouse brain, FACS-sorted mouse brain endothelial cells, and single cell sequencing of mouse brain hippocampus, we revealed the key molecular alteration of endothelial cells characterized by increased Myc targets and Epithelial-Mesenchymal Transition signatures. In addition, immunofluorescence staining of patients' samples confirmed that IGFBP7 was up-regulated in vasculature in response to TBI. TGFβ1, mainly derived from microglia and endothelial cells, sufficiently induces IGFBP7 expression in cultured endothelial cells, and is significantly upregulated in response to TBI. Our results identified IGFBP7 as a potential biomarker of vasculature in response to TBI, and indicate that TGFβ signaling may contribute to the upregulation of IGFBP7 in the vasculature.
血管系统在创伤性脑损伤（TBI）的发病机制和神经修复中起着关键作用。然而，血管内皮细胞在分子水平上如何应对TBI尚未得到系统的综述。在这里，通过整合三个转录组数据集，包括小鼠全脑皮层、荧光激活细胞分选的小鼠脑内皮细胞以及小鼠脑海马体的单细胞测序，我们揭示了以Myc靶点增加和上皮-间质转化特征为特点的内皮细胞关键分子改变。此外，患者样本的免疫荧光染色证实，IGFBP7在TBI反应中在血管系统中上调。TGFβ1主要来源于小胶质细胞和内皮细胞，能充分诱导培养的内皮细胞中IGFBP7的表达，并且在TBI反应中显著上调。我们的结果确定IGFBP7是血管系统对TBI反应的潜在生物标志物，并表明TGFβ信号可能促成血管系统中IGFBP7的上调。
