MALAT1 improves functional recovery after traumatic brain injury through promoting angiogenesis in experimental mice

Abstract

As a highly evolutionary conserved lncRNA, MALAT1 was first demonstrated to associate with metastasis of lung tumor by promoting angiogenesis. Activated vasculature was recently indicated to assist neurogenesis by secreting neurotrophic factor Ang1 (Angiopoietin-1). The purpose of this study is to investigate the potential role of MALAT1 in angiogenesis following traumatic brain injury (TBI). Adult male mice were subjected to controlled cortical impact (CCI) and brain microvascular endothelial cells were exposed to oxygen-glucose deprivation (OGD). MALAT1 RNA levels were quantified by qRT-PCR in different cells of CNS and located by RNA-FISH. Angiogenesis were measured by cell viability, migration assay, tube formation assay in vitro, and immunohistochemistry in vivo. Expression of Angiopoietin-1 was assessed by Western blot. Neurological functions were performed by NSS, Wire grip and MWM tests. Our results indicated that 1) MALAT1 RNA was localized in cerebral endothelium, enhanced by OGD stimuli. 2) Inhibition of MALAT1 by siRNA suppressed angiogenesis, as indicated by endothelial viability, tube formation, migration, and functional vessel density. 3) MALAT1 inhibition further decreased Ang1 expression in the endothelium. 4) Mice with MALAT1 inhibition exhibited worse behavioral performances (NSS, wire grip, Morris water maze), as compared to control. MALAT1 could promote angiogenesis, subsequently contributing to the Ang1 synthesis from active vasculature. It may eventually benefit to functional recovery following TBI.