ABSTRACT
Aims: In previous studies, numerous differential lncRNAs in cerebral ischemic reperfusion injury were identified using RNA-Seq analysis. However, little is known about whether and how lncRNAs involved in cerebral I/R injury. In this study, we investigated the function and explored the possible mechanism of lncRNA Gm11974 in cerebral I/R injury. Methods: Oxygen glucose deprivation model in N2a cells were utilized to mimic the cerebral I/R injury in vitro. Trypan blue staining, Tunel, JC-1 and cell viability were measured to evaluate the function of lncRNA Gm11974. Dual-luciferase reporter assay was used to explore the potential mechanism of lncRNA Gm11974. Results: Gm11974 was mainly located in cytoplasm. Knockdown of lncRNA Gm11974 alleviated the apoptosis induced by OGD and cell death rates were significantly reduced. We further provided the possible mechanism that Gm11974/miR-766-3p/NR3C2 axis plays important role in cerebral I/R injury. Conclusions: We evaluated the function and mechanism of lncRNA Gm11974 in ischemic brain injury. LncRNA Gm11974 may serve as a potential target for new therapeutic intervention.
Subject(s)
Brain Ischemia/complications , Gene Knockdown Techniques , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Receptors, Mineralocorticoid/metabolism , Reperfusion Injury/prevention & control , Base Sequence , Cell Hypoxia/genetics , Glucose/metabolism , HEK293 Cells , Humans , Oxygen/metabolism , RNA, Long Noncoding/metabolism , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/pathologyABSTRACT
BACKGROUND: The development of collateral vessels, which is important to prevent ischemic tissues from cell death, is impaired in patients with diabetes mellitus. The process is regulated by many positive and negative factors. The purpose of the study is to test the hypothesis that stroke patients with diabetes have angiogenesis deficiency and the possible mechanism is hyperglycemia attenuates neovascularization by downregulating proliferative properties of vascular endothelial growth factor (VEGF) and upregulating negative properties of angiostatin. METHODS: Diabetes groups [Goto-Kakizaki (GK)] and respective controls (Wistar rats) underwent 1.5h of middle cerebral artery occlusion (MCAO) and then reperfused for 24h and 7d. Immunohistochemistry was used to describe the change of vessel density. The expression levels of VEGF and angiostatin were estimated by western blot. RESULTS: Compared with the controls, the diabetes groups had lower vessel density, more expression of angiostatin, and lower level of VEGF. CONCLUSIONS: These results showed angiogenesis was deficient in diabetes groups after ischemic reperfusion (I/R) injury. And the possible mechanism is hyperglycemia attenuates neovascularization by downregulating proliferative properties of VEGF and upregulating of negative properties of angiostatin.
