An Integrated Transcriptome Analysis Reveals IGFBP7 Upregulation in Vasculature in Traumatic Brain Injury.

Qiyuan He,Jiefu Tang,Xiangyi Deng,Lei Zhang,Jianhao Wang,Liqun He,Qingze Cao,Fan Yang,Ziwei Zhou,Yuan Xie

doi:10.3389/fgene.2020.599834

Abstract

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.

Highlights

Traumatic brain injury (TBI), one of the leading cause of morbidity and disability, accounts for 30% of all injury-related deaths (Maas et al, 2008)
Direct disruption of cerebral vasculature at the time of head impact leads to hemorrhage and blood flow abnormalities immediately after trauma, and dysfunction of vasculature leads to additional insults such as hypoxemia, hypoxia, hypoperfusion, ischemia, and blood brain barrier (BBB) breakdown (Jullienne et al, 2016)
We focus on the gene expression changes in the brain vascular endothelial cells (EC) under traumatic brain injury (TBI) condition

Summary

Introduction

Traumatic brain injury (TBI), one of the leading cause of morbidity and disability, accounts for 30% of all injury-related deaths (Maas et al, 2008). TBI is a complicated pathophysiological process that can be divided into primary and secondary brain injuries (Sun et al, 2017). Primary injury is the direct damage of neural tissue caused by mechanical effect occurring at the moment of trauma (Silverberg et al, 2019). Secondary brain injury is mediated by several cellular and molecular pathways including excitotoxicity, inflammation, oxidative stress, and energy failure, and cerebral vasculature is a critical player to regulate these pathological processes (Jassam et al, 2017; Salehi et al, 2017; Simon et al, 2017). Direct disruption of cerebral vasculature at the time of head impact leads to hemorrhage and blood flow abnormalities immediately after trauma, and dysfunction of vasculature leads to additional insults such as hypoxemia, hypoxia, hypoperfusion, ischemia, and blood brain barrier (BBB) breakdown (Jullienne et al, 2016)

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Conclusion