环状RNA PPP1CC通过激活HMGB1/TLR9/AIM2途径促进脂多糖诱导的血管平滑肌细胞焦亡。

Circular RNA PPP1CC promotes -lipopolysaccharide-induced pyroptosis of vascular smooth muscle cells by activating the HMGB1/TLR9/AIM2 pathway.

作者信息

Liu Jie, Wang Yong, Liao Yaoyun, Zhou Ying, Zhu Jijin

机构信息

Health Care Department, Liuzhou People's Hospital, Liuzhou city, Guangxi Province, China.

Emergency Department, The First Affiliated Hospital of Guangxi Medical University, Nanning city, Guangxi Province, China.

出版信息

J Int Med Res. 2021 Mar;49(3):300060521996564. doi: 10.1177/0300060521996564.

OBJECTIVE

() plays a critical role in the occurrence and development of atherosclerosis. Lipopolysaccharide from (-LPS) could lead to pyroptosis of vascular smooth muscle cells (VSMCs) and induce instability of atherosclerotic plaque. Therefore, pyroptosis of VSMCs could promote the process of atherosclerosis. However, the exact mechanism of -LPS-induced pyroptosis of VSMCs is unclear.

METHODS

We determined pyroptosis and expression of interleukin (IL)-1β and IL-18 in VSMCs using 4',6-diamidino-2-phenylindole staining and ELISA after stimulation by -LPS. We established a knockdown plasmid containing the circular (circ)RNA PPP1CC and transfected it into VSMCs. Luciferase assays were performed to reveal the association between microRNAs miR-103a-3p and miR-107 and circRNA PPP1CC.

RESULTS

Stimulation of -LPS led to pyroptosis of VSMCs. Knockdown of circRNA PPP1CC relieved the -LPS-induced pyroptosis of VSMCs and suppressed the expression of , , , and cleaved caspase-1. Luciferase assays showed that PPP1CC directly targeted and competitively adsorbed miR-103a-3p and miR-107, weakening the inhibitory effect of these microRNAs on the expression of .

CONCLUSION

Knockdown of circRNA PPP1CC relieved -LPS-induced pyroptosis of VSMCs. Pyroptosis of VSMCs appears to promote atherosclerosis and may represent a novel therapeutic target for its treatment.

目的

（）在动脉粥样硬化的发生和发展中起关键作用。来自（-LPS）的脂多糖可导致血管平滑肌细胞（VSMC）发生焦亡，并诱导动脉粥样硬化斑块不稳定。因此，VSMC的焦亡可促进动脉粥样硬化进程。然而，-LPS诱导VSMC焦亡的确切机制尚不清楚。

方法

在用-LPS刺激后，我们使用4',6-二脒基-2-苯基吲哚染色和酶联免疫吸附测定法（ELISA）测定VSMC中的焦亡以及白细胞介素（IL）-1β和IL-18的表达。我们构建了一个包含环状（circ）RNA PPP1CC的敲低质粒，并将其转染到VSMC中。进行荧光素酶测定以揭示微小RNA miR-103a-3p和miR-107与circRNA PPP1CC之间的关联。

结果

-LPS刺激导致VSMC发生焦亡。敲低circRNA PPP1CC可减轻-LPS诱导的VSMC焦亡，并抑制（此处原文缺失相关基因名称）、（此处原文缺失相关基因名称）、（此处原文缺失相关基因名称）和裂解的半胱天冬酶-1的表达。荧光素酶测定表明，PPP1CC直接靶向并竞争性吸附miR-103a-3p和miR-107，削弱了这些微小RNA对（此处原文缺失相关基因名称）表达的抑制作用。