LncRNA SNHG4 Attenuates Inflammatory Responses by Sponging miR-449c-5p and Up-Regulating STAT6 in Microglial During Cerebral Ischemia-Reperfusion Injury

• Published in: Drug design, development and therapy development and therapy, 2020-01, Vol.14, p.3683-3695
• Main Authors: Zhang, Shuo, Sun, Wen-Chong, Liang, Zuo-di, Yin, Xiu-Ru, Ji, Zhen-Rong, Chen, Xiao-Huan, Wei, Min-Jie, Pei, Ling
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Brain Ischemia - metabolism; Brain Ischemia - pathology; Carotid arteries; Cells, Cultured; Cerebral blood flow; Cerebral infarction; Cerebral ischemia; Cerebrospinal fluid; Computer simulation; Crosstalk; Cytokines; Deprivation; Experiments; Glucose; Hospitals; Humans; In vivo methods and tests; Infarction; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammatory response; Injuries; Ischemia; ischemia-reperfusion injury; Laboratory animals; Lipopolysaccharides; Male; Microglia; Microglia - metabolism; Microglia - pathology; MicroRNAs - genetics; MicroRNAs - metabolism; mir-449c-5p; Occlusion; Original Research; Overexpression; Oxygen; Rats; Rats, Sprague-Dawley; Reagents; Reperfusion; Reperfusion injury; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; snhg4; stat6; Stat6 protein; STAT6 Transcription Factor - genetics; STAT6 Transcription Factor - metabolism; Stroke; Traumatic brain injury; Tumor necrosis factor-TNF; Up-Regulation; Veins & arteries
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S245445

Inflammatory response mediated by microglia plays a key role in cerebral ischemia-reperfusion injury. This study intends to probe the role of lncRNA SNHG4 in regulating the inflammatory response of the microglia during cerebral ischemia reperfusion. Blood samples and cerebrospinal fluid samples were collected from acute cerebral infarction (ACI) patients and healthy controls. The middle cerebral artery occlusion (MCAO) models were constructed with rats. LPS induction and oxygen-glucose deprivation methods were respectively applied to simulate the activation of microglia in vitro. qRT-PCR was employed to determine the expressions of SNHG4, miR-449c-5p and related inflammatory factors in vivo and in vitro. The inflammatory responses of the microglia subject to the varied expressions of SNHG4 and miR-449c-5p were detected. Luciferase assays were conducted to verify the crosstalk involving SNHG4, miR-449c-5p and STAT6. Compared with the control group, the expression of SNHG4 derived from the samples of ACI patients and the microglia of MCAO group were remarkably down-regulated, but the expression of miR-449c-5p was dramatically up-regulated. Overexpression of SNHG4 and knock-down of miR-449c-5p could inhibit the expression of pro-inflammatory cytokine in the microglia and promote the expression of anti-inflammatory factors. Meanwhile, the phospho-STAT6 was up-regulated, whereas the knock-down of SNHG4 and over-expression of miR-449c-5p in microglia had the opposite effects. Luciferase assay confirmed that SNHG4 could target miR-449c-5p, while miR-449c-5p could target STAT6. SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury.