Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus
Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus
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鉴定长非编码 RNA NEAT1 作为通过 MAPK 通路在人类狼疮中发挥作用的新型炎症调节因子
DOI：
10.1016/j.jaut.2016.07.012
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发表时间：
2016-12-01
影响因子：
12.8
通讯作者：
Tang, Yuanjia
中科院分区：
文献类型：
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作者：
Zhang, Feifei;Wu, Lingling;Tang, Yuanjia
长链非编码RNA（IncRNA）与多种人类疾病密切相关。然而，我们对系统性红斑狼疮（SLE）相关lncRNA的了解仍然有限。在本研究中，我们研究了IncRNA NEAT 1在SLE发病机制中的作用。在这里，我们发现NEAT 1的表达异常增加，在SLE患者和主要表达在人单核细胞。此外，NEAT 1表达由LPS通过p38激活诱导。沉默NEAT 1显著降低了一组趋化因子和细胞因子的表达，包括IL-6、CXCL 10等，LPS持续诱导晚期细胞凋亡。此外，NEAT 1通过影响晚期MAPK信号通路的激活而参与TLR 4介导的炎症过程。重要的是，NEAT 1与SLE患者的临床疾病活动性呈正相关。总之，NEAT 1表达的增加可能是SLE患者中许多细胞因子和趋化因子产生增加的潜在因素。我们的研究结果表明，IncRNA有助于狼疮的发病机制，并为治疗干预提供了潜在的新靶点。(C)2016爱思唯尔有限公司版权所有
Long noncoding RNAs (IncRNAs) have recently been identified to be tightly linked to diverse human diseases. However, our knowledge of Systemic Lupus Erythematosus (SLE)-related lncRNAs remains limited. In the present study we investigated the contribution of the IncRNA NEAT1 to the pathogenesis of SLE. Here, we found NEAT1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, NEAT1 expression was induced by LPS via p38 activation. Silencing NEAT1 significantly reduced the expression of a group of chemokines and cytokines, including IL-6, CXCL10, etc., which were induced by LPS continuously and in late stages. Furthermore, it was identified the involvement of NEAT1 in TLR4-mediated inflammatory process was through affecting the activation of the late MAPK signaling pathway. Importantly, there was a positive correlation between NEAT1 and clinical disease activity in SLE patients. In conclusion, the increased NEAT1 expression may be a potential contributor to the elevated production of a number of cytokines and chemokines in SLE patients. Our findings suggest IncRNA contributes to the pathogenesis of lupus and provides potentially novel target for therapeutic intervention. (C) 2016 Elsevier Ltd. All rights reserved.