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MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3

机译:MiRNA-532-5P通过靶向Stat3调节Cums诱导的抑郁类行为,并调节LPS诱导的促炎细胞因子信号传导

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Background:It is known that miR-532-5p is critical for neuronal differentiation. However, the role of miR-532-5p in depression remains unknown. This study aimed to investigate the role and mechanism of miR-532-5p in major depressive disorder (MDD).Methods:The depression mice model was established by chronic unpredictable mild stress (CUMS) and confirmed by forced swimming test (FST) and sucrose preference test (SPT). The role of miR-532-5p in MDD was detected by tail suspension test (TST), FST, SPT and SIT. QRT-PCR was used to detect the expression of miR-139-5p in hippocampus and BV-2 microglia of mice. ELISA and Western blotting were used to detect the expression of the nitric oxide synthase (NOS), proinflammatory cytokines (IL-6, IL-1β, TNF-α, and MCP-1) and transcriptional activator 3 (STAT3). Luciferase reporter assay was used to verify the downstream target genes of miR-532-5p.Results:MiR-532-5p was significantly reduced in the hippocampus of mice treated with CUMS. Overexpression of miR-532-5p significantly reduced CUMS-induced depression-like behaviors and suppressed the expression of IL-6, IL-1β, TNF-α and MCP-1. MiR-532-5p directly targeted signal transducers and STAT3 in BV2 cells. In addition, overexpression of miR-532-5p restrained the raise of inducible NOS and IL-6, IL-1 β, TNF-α and MCP-1 in LPS-exposed BV2 cells.Conclusion:This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy.? 2020 Yan et al.
机译:背景:已知MiR-532-5P对于神经元分化至关重要。然而,MIR-532-5P在抑郁症中的作用仍然未知。本研究旨在探讨miR-532-5p在重大抑郁症(mdd)中的作用和机制。方法:抑郁小鼠模型由慢性不可预测的温和胁迫(CUMS)建立,并通过强制游泳试验(FST)和蔗糖证实偏好测试(SPT)。 MIR-532-5P在MDD中的作用被尾悬架试验(TST),FST,SPT和坐下来检测。 QRT-PCR用于检测海马和BV-2小鼠的MiR-139-5P的表达。 ELISA和Western印迹用于检测一氧化氮合酶(NOS),促炎细胞因子(IL-6,IL-1β,TNF-α和MCP-1)和转录活化剂3(STAT3)的表达。荧光素酶报告结果用于验证miR-532-5p.results的下游靶基因:MiR-532-5p在用CUMS处理的小鼠的海马中显着降低。 miR-532-5p的过表达显着减少了CUMS诱导的抑郁症行为,并抑制了IL-6,IL-1β,TNF-α和MCP-1的表达。 miR-532-5p直接有针对性的信号传感器和BV2细胞中的STAT3。此外,miR-532-5p的过表达抑制了LPS-暴露的BV2细胞中的诱导NoS和IL-6,IL-1β,TNF-α和MCP-1的升高。结论:该研究表明miR-532-通过靶向STAT3,5P在CUMS诱导的抑郁症行为中起重要作用,MIR-532-5P可能是MDD治疗的潜在目标。 2020年yan等人。

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