circACTA2 inhibits NLRP3 inflammasome-mediated inflammation via interacting with NF-κB in vascular smooth muscle cells.
circACTA2 inhibits NLRP3 inflammasome-mediated inflammation via interacting with NF-κB in vascular smooth muscle cells.
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circACTA2通过与血管平滑肌细胞NF-κB相互作用抑制NLRP3炎症小体介导的炎症。
DOI：
10.1007/s00018-023-04840-6
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发表时间：
2023-07-27
影响因子：
8
通讯作者：
Wen, Jinkun
中科院分区：
文献类型：
--
作者：
Bai, Yang;Zhang, Long;Zheng, Bin;Zhang, Xinhua;Zhang, Hong;Zhao, Anning;Yu, Jing;Yang, Zhan;Wen, Jinkun
circACTA2 derived from the smooth muscle α-actin gene plays an important role in the regulation of vascular smooth muscle cell (VSMC) phenotype. The activation of NLRP3 inflammasome is involved in VSMC phenotypic switching. However, the mechanistic relationship between circACTA2 and NLRP3 inflammasome during vascular remodeling remains poorly understood. Here, we showed that circACTA2 was down-regulated in human intimal hyperplasia. circACTA2 overexpression in circACTA2 transgenic mice significantly decreased the neointimal hyperplasia induced by vascular injury, which is concomitant with a decrease in IL-18, IL-1β, TNF-α, and IL-6 levels. Gain- and loss-of-function studies revealed that circACTA2 alleviated VSMC inflammation by suppressing the activation of NLRP3 inflammasome. Mechanistically, circACTA2 inhibited the expression of NF-κB p65 and p50 subunits and interacted with p50, which impedes the formation of the p50/p65 heterodimer and nuclear translocation induced by TNF-α, thus resulting in the suppression of NLRP3 gene transcription and inflammasome activation. Furthermore, circACTA2 overexpression mitigated inflammation via repressing NLRP3 inflammasome-mediated VSMC pyroptosis. Importantly, employing a decoy oligonucleotide to compete with circACTA2 for binding to p50 could attenuate the expression of NLRP3, ASC, and caspase-1. These findings provide a novel insight into the functional roles of circACTA2 in VSMCs, and targeting the circACTA2–NF-κB–NLRP3 axis represents a promising therapeutic strategy for vascular remodeling. The online version contains supplementary material available at 10.1007/s00018-023-04840-6.
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影响因子：
7.3
作者：
Chen S;Tang C;Ding H;Wang Z;Liu X;Chai Y;Jiang W;Han Y;Zeng H
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
11.4
作者：
Jia, Yifan;Cui, Ruixia;Zhang, Jingyao
通讯作者：
Zhang, Jingyao
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影响因子：
10.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.2019604117
发表时间：
2020-11-24
影响因子：
11.1
作者：
Kravtsova-Ivantsiv, Yelena;Goldhirsh, Gilad;Ciechanover, Aaron
通讯作者：
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