Long non-coding RNA RP11-490M8.1 inhibits lipopolysaccharide-induced pyroptosis of human umbilical vein endothelial cells via the TLR4/NF-κB pathway,Immunobiology

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Long non-coding RNA RP11-490M8.1 inhibits lipopolysaccharide-induced pyroptosis of human umbilical vein endothelial cells via the TLR4/NF-κB pathway
Immunobiology ( IF 2.5 ) Pub Date : 2021-08-27 , DOI: 10.1016/j.imbio.2021.152133
Xue-Hui Liu ₁ , Li-Mei Wu ₂ , Jia-Li Wang ₃ , Xian-Hui Dong ₄ , Shun-Chi Zhang ₂ , Xue-Heng Li ₅ , Hui Xu ₆ , Da-Bin Liu ₂ , Zhi-Hai Li ₂ , Zhe-Ming Liu ₇ , Shao-Guo Wu ₂ , Yan-Wei Hu ₈

Affiliation

Department of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou, Guangdong 510620, China.
Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou, Guangdong 510620, China.
Department of Blood Transfusion, Linyi People's Hospital of Shandong Province, Linyi, ShanDong 276000, China.
Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, China.
Department of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Traditional Chinese Medical Hospital of Qingyuan, Qingyuan, Guangdong 511500, China.
Stomatology Major, Medical College of Jinzhou Medical University, Jinzhou, Liaoning, China.
Department of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, China.

Background and aims

Pyroptosis is a relatively newly discovered form of programmed cell death that plays an important role in the development of atherosclerosis. Many studies have reported that lncRNAs participated in the regulation of atherosclerosis development. However, the regulatory mechanism of lncRNAs in pyroptosis must be studied further.

Methods

In a previous study, microarray analysis was used to detect the lncRNA expression profile in three human advanced atherosclerotic plaques and three normal arterial intimae. In the present research, in vitro assays were performed to investigate the role of lncRNA RP11-490M8.1 on pyroptosis. The relative gene mRNA and lncRNA expression levels were tested by quantitative real-time PCR, and protein levels were evaluated by western blot analysis. The RNA hybrid structure was analyzed using the DINAMelt server.

Results

The lncRNA RP11-490M8.1 was significantly downregulated in atherosclerotic plaques and serum. Lipopolysaccharide (LPS) markedly reduced the expression of lncRNA RP11-490M8.1 and induced pyroptosis by increasing the mRNA and protein levels of NLRP3, caspase-1, ASC, IL-1β, and IL-18 in HUVECs. The promotion effects of LPS on pyroptosis were markedly suppressed by overexpression of lncRNA RP11-490M8.1. In addition, LPS increased the mRNA and protein levels of TLR4 and NF-κB, which was also markedly offset by overexpression of lncRNA RP11-490M8.1.

Conclusions

These findings indicated that lncRNA RP11-490M8.1 inhibited LPS-induced pyroptosis via the TLR4/NF-κB pathway. Thus, lncRNA RP11-490M8.1 may provide a therapeutic target to ameliorate atherosclerosis.

中文翻译：

长链非编码RNA RP11-490M8.1通过TLR4/NF-κB通路抑制脂多糖诱导的人脐静脉内皮细胞焦亡

背景和目标

焦亡是一种相对较新发现的程序性细胞死亡形式，在动脉粥样硬化的发展中起重要作用。许多研究报道lncRNA参与了动脉粥样硬化发展的调控。然而，lncRNAs 在细胞焦亡中的调控机制仍需进一步研究。

方法

在之前的一项研究中，微阵列分析用于检测三个人类晚期动脉粥样硬化斑块和三个正常动脉内膜中的 lncRNA 表达谱。在本研究中，进行了体外测定以研究 lncRNA RP11-490M8.1 对细胞焦亡的作用。通过定量实时PCR测试相对基因mRNA和lncRNA表达水平，并通过蛋白质印迹分析评估蛋白质水平。使用 DINAMelt 服务器分析 RNA 杂交结构。

结果

lncRNA RP11-490M8.1在动脉粥样硬化斑块和血清中显着下调。脂多糖 (LPS) 通过增加HUVECs 中 NLRP3、caspase-1、ASC、IL-1β 和 IL-18 的 mRNA 和蛋白水平显着降低 lncRNA RP11-490M8.1 的表达并诱导细胞焦亡。 lncRNA RP11-490M8.1的过表达显着抑制了LPS对细胞焦亡的促进作用。此外，LPS 增加了 TLR4 和 NF-κB 的 mRNA 和蛋白质水平，这也被 lncRNA RP11-490M8.1 的过表达显着抵消。