Upregulation of microRNA-206 enhances lipopolysaccharide-induced inflammation and release of amyloid-β by targeting insulin-like growth factor 1 in microglia

• Published in: Molecular medicine reports Vol. 14; no. 2; pp. 1357 - 1364
• Main Authors: Xing, Hongxia, Guo, Shuangxi, Zhang, Yi, Zheng, Zhiyong, Wang, Haoliang
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.08.2016; Spandidos Publications UK Ltd
• Subjects: 3' Untranslated Regions; Age; Aged; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; amyloid-β; Binding Sites; Case-Control Studies; Cell Line; Cells, Cultured; Cytokines; Cytokines - metabolism; Female; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators - metabolism; Insulin; insulin-like growth factor 1; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Male; Microglia; Microglia - drug effects; Microglia - metabolism; microRNA; MicroRNAs - genetics; miRNA; Neurodegenerative diseases; Neurogenesis; neuroinflammation; Neuroprotection; Neurotoxicity; Older people; Peripheral blood; Polymerase chain reaction; Reporter gene; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signal transduction; Tumor necrosis factor-TNF; Up-regulation; β-Amyloid; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.5369

Activated microglia are capable of facilitating amyloid-β (Aβ) accumulation via the release of inflammatory factors, thus resulting in the exacerbation of Alzheimer's disease (AD). MicroRNAs (miRs) participate in the activation of microglia, which is associated with AD. Insulin-like growth factor 1 (IGF1) is a neuroprotective, anti-inflammatory factor, which is able to accelerate clearance of Aβ peptides. The present study aimed to investigate the precise role of miR-206 and IGF1 in lipopolysaccharide (LPS)-induced microglial inflammation. The expression levels of miR-206 and IGF1 were detected in 60 peripheral blood samples from patients with AD and matched age subjects using quantitative polymerase chain reaction. A dual luciferase reporter gene assay was used to indicate the relationship between miR-206 and IGF1. In addition, the role of miR-206 was determined by gain and loss of function experiments in LPS-treated microglia. The results demonstrated that miR-206 upregulation enhanced LPS-induced inflammation and Aβ release in microglia by directly targeting the 3′-untranslated region of IGF1. These effects were attenuated following treatment with exogenous IGF1, thus indicating that the miR-206/IGF1 signaling pathway may be considered a novel therapeutic target for the treatment of AD-associated microglial inflammation.