长链非编码 RNA H19 通过靶向 miR-29b/C1QTNF6 轴促进缺血性脑卒中时的白细胞炎症反应。

Long non-coding RNA H19 promotes leukocyte inflammation in ischemic stroke by targeting the miR-29b/C1QTNF6 axis.

机构信息

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Institute of Integrative Medicine, Qingdao University, Qingdao, China.

出版信息

CNS Neurosci Ther. 2022 Jun;28(6):953-963. doi: 10.1111/cns.13829. Epub 2022 Mar 24.

AIMS

Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non-coding RNA (lncRNA) H19-mediated regulation of C1q and tumor necrosis factor 6 (C1QTNF6) by sponging miR-29b in leukocytes during ischemic stroke.

METHODS

H19 and miR-29b expression in leukocytes of patients with ischemic stroke and rats with middle cerebral artery occlusion were measured by real-time polymerase chain reaction. H19 siRNA and miR-29b antagomir were used to knock down H19 and miR-29b, respectively. We performed in vivo and in vitro experiments to determine the impact of H19 and miR-29b on C1QTNF6 expression in leukocytes after ischemic injury.

RESULTS

H19 and C1QTNF6 upregulation, as well as miR-29b downregulation, was detected in leukocytes of patients with stroke. Moreover, miR-29b could bind C1QTNF6 mRNA and repress its expression, while H19 could sponge miR-29b to maintain C1QTNF6 expression. C1QTNF6 overexpression promoted the release of IL-1β and TNF-α in leukocytes, further exacerbated blood-brain barrier disruption, and aggravated the cerebral ischemic injury.

CONCLUSIONS

Our findings confirm that H19 promotes leukocyte inflammation by targeting the miR-29b/C1QTNF6 axis in cerebral ischemic injury.

目的

白细胞引起的炎症反应在急性缺血性脑卒中的病理生理学中起着至关重要的作用。本研究旨在阐明长链非编码 RNA（lncRNA）H19 通过海绵吸附 miR-29b 调节缺血性中风期间白细胞中 C1q 和肿瘤坏死因子 6（C1QTNF6）的炎症机制。

方法

通过实时聚合酶链反应测量缺血性中风患者和大脑中动脉闭塞大鼠白细胞中的 H19 和 miR-29b 表达。使用 H19 siRNA 和 miR-29b 拮抗剂分别敲低 H19 和 miR-29b。我们进行了体内和体外实验，以确定 H19 和 miR-29b 对缺血性损伤后白细胞中 C1QTNF6 表达的影响。

结果

在中风患者的白细胞中检测到 H19 和 C1QTNF6 的上调以及 miR-29b 的下调。此外，miR-29b 可以结合 C1QTNF6 mRNA 并抑制其表达，而 H19 可以通过海绵吸附 miR-29b 来维持 C1QTNF6 的表达。C1QTNF6 的过表达促进了白细胞中 IL-1β 和 TNF-α 的释放，进一步加重了血脑屏障的破坏，并加重了脑缺血损伤。