miR-137 alleviates focal cerebral ischemic injury in rats by regulating JAK1/STAT1 signaling pathway

• Published in: Human & experimental toxicology 2020-06, Vol.39 (6), p.816-827
• Main Authors: Zhang, M, Ge, DJ, Su, Z, Qi, B
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Brain; Brain - metabolism; Brain - pathology; Brain damage; Brain injury; Cell proliferation; Cells, Cultured; Cerebral infarction; Cytokines - metabolism; Deprivation; DNA nucleotidylexotransferase; Enzyme-linked immunosorbent assay; Glucose; Hippocampus; IL-1β; Infarction; Infarction, Middle Cerebral Artery - genetics; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Inflammation; Injuries; Interleukin 6; Ischemia; Janus kinase; Janus Kinase 1 - metabolism; Male; MicroRNAs; Moisture content; Neurons; Neurons - metabolism; Neurons - pathology; Oxygen; Polymerase chain reaction; Proteins; Rats, Sprague-Dawley; Reverse transcription; Signal Transduction; Staining; Stat1 protein; STAT1 Transcription Factor - metabolism; Tissues; Transfection; Triphenyltetrazolium chloride; Tumor necrosis factor-α; Water content
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327119897103

The repairing effect and potential mechanism of miR-137 on cerebral ischemic injury in rats was investigated. The volume of cerebral infarction and calculated brain water content was detected by triphenyltetrazolium chloride staining. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay. The pathological damage of brain tissue was analyzed by hematoxylin and eosin and Nissl staining. The apoptosis in ischemic brain tissue was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The levels of STAT1 and JAK1 proteins were analyzed by Western blot. The expression of miR-137 in primary hippocampal neurons was detected by reverse transcription polymerase chain reaction. miR-137 overexpression significantly improved brain damage in rats. miR-137 overexpression can reduce the expression of TNF-α, IL-1β, and IL-6. miR-137 overexpression can reduce the degree of brain tissue damage and inhibit the expression of JAK1 and STAT1 proteins. miR-137 overexpression can reduce oxygen-glucose deprivation (OGD)/R-induced cell damage, improve cell proliferation, and reduce apoptotic rate. JAK1 and STAT1 protein expression was inhibited in hippocampal neurons after OGD/R treatment after transfection with miR-137 mimic. After the addition of the Filgotinib inhibitor, the levels of JAK1 and STAT1 proteins were significantly reduced. The results suggested that miR-137 overexpression can effectively improve ischemic injury after focal cerebral ischemia and protect against by inhibiting JAK1/STAT1 pathway.