CircRNA-3302 promotes endothelial-to-mesenchymal transition via sponging miR-135b-5p to enhance KIT expression in Kawasaki disease.
CircRNA-3302 promotes endothelial-to-mesenchymal transition via sponging miR-135b-5p to enhance KIT expression in Kawasaki disease.
复制标题
DOI：
10.1038/s41420-022-01092-4
复制
发表时间：
2022-06-29
影响因子：
7
通讯作者：
Jia C
中科院分区：
文献类型：
--
作者：
Ni C;Qiu H;Zhang S;Zhang Q;Zhang R;Zhou J;Zhu J;Niu C;Wu R;Shao C;Mamun AA;Han B;Chu M;Jia C
内皮细胞向间质细胞转化（EndMT）参与了肌纤维母细胞样细胞介导的对川崎患者冠状动脉壁的损伤，从而增加了冠状动脉瘤的风险。许多环状RNA（circRNA）已被报道与心血管疾病相关。然而，circRNA在KD相关EndMT中的作用和潜在的分子机制仍然不确定。在本研究中，我们通过circRNA测序（circRNA-seq）从健康对照（HC）或KD患者血清处理的人脐静脉内皮细胞（HUVECs）中筛选出circRNA-3302。此外，在由KD血清刺激的内皮细胞和用白色念珠菌细胞壁提取物（CAWS）建模的病理性KD小鼠中证实了circRNA-3302上调。此外，体外实验表明，circRNA-3302的过表达可显著诱导EndMT，而circRNA-3302的沉默可显著减轻KD血清介导的EndMT。为了进一步探讨circRNA-3302诱导EndMT的分子机制，本研究采用RNA测序（RNA-seq）、双荧光素酶报告系统、核内和核外RNA提取、RT-qPCR和Western blot分析等方法。我们的数据表明，circRNA-3302通过海绵状的miR-135 b-5 p来增强KIT表达，从而促进KD相关的EndMT。总的来说，我们的研究结果表明，circRNA-3302在KD相关的EndMT中起着重要作用，为最大限度地降低冠状动脉瘤的风险提供了新的见解。
Endothelial-to-mesenchymal transition (EndMT) is implicated in myofibroblast-like cell-mediated damage to coronary artery wall of Kawasaki disease (KD) patients, which subsequently increases the risk of coronary artery aneurysm. Many circular RNAs (circRNAs) have been reported to be associated with cardiovascular diseases. However, the roles and underlying molecular mechanism of circRNAs in KD-associated EndMT remains indefinite. In this research, we screened out circRNA-3302 from human umbilical vein endothelial cells (HUVECs) treated by sera from healthy controls (HCs) or KD patients via circRNA sequencing (circRNA-seq). In addition, circRNA-3302 upregulation was verified in endothelial cells stimulated by KD serum and pathological KD mice modeled with Candida albicans cell wall extracts (CAWS). Moreover, in vitro experiments demonstrated that overexpression of circRNA-3302 could markedly induce EndMT, and silencing of circRNA-3302 significantly alleviated KD serum-mediated EndMT. To further explore the molecular mechanisms of circRNA-3302 inducing EndMT, RNA sequencing (RNA-seq), a dual-luciferase reporter system, nuclear and extra-nuclear RNA isolation, RT-qPCR and Western blot analyses and so on, were utilized. Our data demonstrated that circRNA-3302 contributed to the KD-associated EndMT via sponging miR-135b-5p to enhance KIT expression. Collectively, our results imply that circRNA-3302 plays an important role in KD-associated EndMT, providing new insights into minimizing the risks of developing coronary artery aneurysms.
登录
查看更多内容
影响因子：
64.5
作者：
Kleaveland B;Shi CY;Stefano J;Bartel DP
通讯作者：
Bartel DP
IL-37b通过IL-1R8通路减轻川崎病内皮细胞凋亡和炎症
影响因子：
9
作者：
Jia C;Zhuge Y;Zhang S;Ni C;Wang L;Wu R;Niu C;Wen Z;Rong X;Qiu H;Chu M
通讯作者：
Chu M
在致癌 BRAF 诱导的黑色素瘤小鼠模型中体内鉴定肿瘤抑制性 PTEN ceRNA。
影响因子：
64.5
作者：
Karreth FA;Tay Y;Perna D;Ala U;Tan SM;Rust AG;DeNicola G;Webster KA;Weiss D;Perez-Mancera PA;Krauthammer M;Halaban R;Provero P;Adams DJ;Tuveson DA;Pandolfi PP
通讯作者：
Pandolfi PP
内皮细胞焦亡通过 HMGB1/RAGE/cathespin B 信号通路和 NLRP3 炎症小体激活在川崎病中发挥重要作用
影响因子：
9
作者：
Jia, Chang;Zhang, Jian;Chu, Maoping
通讯作者：
Chu, Maoping
DOI：
10.1186/s13046-019-1065-7
发表时间：
2019-02-08
影响因子：
11.3
作者：
He, Zhenwei;Ruan, Xuelei;Xue, Yixue
通讯作者：
Xue, Yixue