Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway (Retracted article. See vol. 98, 2021)
Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway (Retracted article. See vol. 98, 2021)
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DOI：
10.1016/j.intimp.2018.03.023
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发表时间：
2018-06-01
影响因子：
5.6
通讯作者：
Jiang Dongxin
中科院分区：
文献类型：
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作者：
Chen Yi;Qiu Jialing;Jiang Dongxin
本研究旨在探讨非编码长链RNA NEAT1在脓毒症所致急性肾损伤(AKI)中的作用。检测脓毒症所致AKI患者中NEAT1的表达水平。用脂多糖(LPS)诱导大鼠肾小球系膜细胞(RMC)损伤。然后，检测NEAT1抑制对内毒素刺激的RMCs的细胞活力、细胞凋亡率、细胞因子表达和氧化应激的影响。研究了NEAT1的调控miRNA以及该miRNA的靶基因。此外，还探讨了NEAT1与核因子-kappaB通路之间的调控关系。结果表明，在脓毒症诱导的AKI患者中，NEAT1的表达显著上调。此外，在脓毒症患者中，NEAT1的上调与MU的严重程度相关。此外，抑制NEAT1可减轻脂多糖对RMC的损伤作用。MIR-204受NEAT1负调控。抑制NEAT1可通过过表达miR-204减轻内毒素诱导的损伤。此外，IL-6R是miR-204的靶点，抑制NEAT1对内毒素诱导的细胞损伤的作用是通过失活NF-kappa B途径实现的。综上所述，NEAT1的上调可能通过靶向miR-204和激活核因子-kappaB途径而加重内毒素诱导的损伤。NEAT1可作为脓毒症AKI的重要诊断标记物和治疗靶点。
This study aimed to explore the role of long non-coding RNA NEAT1 in sepsis-induced acute kidney injury (AKI). The expression levels of NEAT1 in sepsis-induced AKI patients were detected. The rat mesangial cells (RMCs) were treated with lipopolysaccharide (LPS) to induce cell injury. Then, the effects of NEAT1 suppression on the cell viability, apoptosis, cytokines expression, and oxidative stress in the LPS-stimulated RMCs were tested. The regulatory miRNA of NEAT1, as well as the target genes of this miRNA, were investigated. Moreover, the regulatory relationship between NEAT1 and the NF-kappa B pathway was explored. The results demonstrated that NEAT1 was significantly upregulated in the sepsis-induced AKI patients. Moreover, the upregulation of NEAT1 was associated with the serious degrees of MU in sepsis patients. In addition, the suppression of NEAT1 alleviated LPS-induced injury in RMCs. MiR-204 was negatively regulated by NEAT1. Suppression of NEAT1 alleviated LPS-induced injury by overexpression of miR-204. Moreover, IL-6R was a target of miR-204, and the effects of the suppression of NEAT1 on LPS-induced cell injury were caused by inactivating the NF-kappa B pathway. In conclusion, upregulation of NEAT1 may aggravate the LPS-induced injury by targeting miR-204 and activating the NF-kappa B pathway. NEAT1 may serve as an important diagnostic marker and therapeutic target in sepsis induced AKI.