ChongjieCheng
As a highly evolutionary conserved lncRNA, MALAT1 was first demonstrated to associate with metastasis of lung tumorby promoting angiogenesis. Activated vasculature was recently indicated to assist neurogenesis by secreting neurotrophic factors. The purpose of this study is to explore thepotential role of MALAT1in angiogenesis and neurogenesisfollowingtraumatic brain injury(TBI), as well as its mechanistic connection.The controlled cortical impact (CCI) and oxygen-glucose deprivation (OGD)models were established to mimic neuropathologyof TBI, and siRNA, inhibitior, transgenic mice were used to analyse the effects of MALAT1. Our results indicated that silencing of MALAT1 invitroinhibited endothelialcell viabilityandtubeformation, while increasing migrationability. The mice deficient in MALAT1 exhibited reduced endothelial proliferation, functional vessel density and cerebral blood flow. Furthermore, MALAT1 downregulation suppressed neuroblasts migration, and decreasedendothelial production of SDF-1α and neurovascular coupling niches. RNA pull-down assay validated EZH2 as thedownstream elementof MALAT1.And MALAT1 recruited EZH2 to Notch1 promoter regions and epigenetically promoted Notch1 transcription, independent of H3K27me3 activity. Agonist of Notch1 reverses the MALAT1 deficiency-mediated impaired angiogenesis and neurogenesis. Our results suggest that MALAT1 controls key steps of neurovascular remodeling following TBI in EZH2/NOTCH1-dependent manner.Keywords—Traumatic brain injury; Metastasis associated lung adenocarcinoma transcript 1; Vascular remodeling
