Mechanism of DKK3 protecting brain tissues in ischemic stroke by regulating LGI1 expression and activity.

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

European Journal of Medical Research Pub Date : 2025-10-21 DOI:10.1186/s40001-025-03260-5

DongLiang Zhou, Lei Miao, LinJuan Feng, HongWei Qin, Ying Xu, JianMin Wang

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引用次数: 0

Abstract

Objective: To investigate the mechanism of Dickkopf-3 (DKK3) in protecting brain tissues in ischemic stroke (IS) by regulating LGI1 expression and activity.

Methods: 220 patients with acute ischemic stroke (AIS) were enrolled to measure the serum DKK3 levels and analyze the predictive ability of serum DKK3 for early neurological deterioration (END) in AIS patients. A murine model of permanent middle cerebral artery occlusion (pMCAO) was established. Neurological function recovery in mice was assessed using neurological function scores and behavioral experiments, and the volume of cerebral infarction in mice was measured. The histopathological morphology of the cortex in mice was observed by hematoxylin‒eosin staining; apoptotic neurons were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. DKK3 and leucine-rich glioma-inactivated protein 1 (LGI1) expression levels were measured by immunofluorescence, RT-qPCR, or Western blot, and their interaction was verified by bioinformatics analysis and Co-IP. A cellular model of oxygen-glucose deprivation (OGD) injury was established using HT22 murine neurons for in vitro investigation.

Results: DKK3 was downregulated in IS and shows potential as a biomarker for predicting END in AIS patients. DKK3 overexpression contributed to neurological recovery and attenuated brain injury in pMCAO mice. DKK3 co-localized and interacted with LGI1. LGI1 downregulation weakened the protective effect of DKK3 against pMCAO-induced brain damage and OGD-induced neuronal injury.

Conclusion: DKK3 protects against ischemic injury in permanent cerebral ischemia by regulating LGI1 expression and activity.

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DKK3通过调节LGI1表达和活性对缺血性脑卒中脑组织的保护机制

目的：探讨Dickkopf-3 （DKK3）通过调节LGI1的表达和活性对缺血性脑卒中脑组织的保护作用机制。方法：选取220例急性缺血性脑卒中（AIS）患者，测定血清DKK3水平，分析血清DKK3对AIS患者早期神经功能恶化（END）的预测能力。建立小鼠永久性大脑中动脉闭塞（pMCAO）模型。采用神经功能评分和行为实验评估小鼠神经功能恢复情况，并测量小鼠脑梗死体积。苏木精-伊红染色观察小鼠皮层组织病理形态；用末端脱氧核苷酸转移酶dUTP缺口端标记法观察凋亡神经元的变化。通过免疫荧光、RT-qPCR或Western blot检测DKK3和富含亮氨酸的胶质瘤失活蛋白1 （LGI1）的表达水平，并通过生物信息学分析和Co-IP验证它们的相互作用。采用HT22小鼠神经元建立氧糖剥夺（OGD）损伤细胞模型，进行体外研究。结果：DKK3在IS中下调，显示出作为预测AIS患者END的生物标志物的潜力。DKK3过表达有助于pMCAO小鼠神经功能恢复和脑损伤减轻。DKK3与LGI1共定位并相互作用。LGI1下调减弱了DKK3对pmcao诱导的脑损伤和ogd诱导的神经元损伤的保护作用。结论：DKK3通过调节LGI1的表达和活性，对永久性脑缺血的缺血性损伤具有保护作用。

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来源期刊

European Journal of Medical Research 医学-医学：研究与实验

CiteScore

3.20

自引率

0.00%

发文量

247

审稿时长

>12 weeks

期刊介绍： European Journal of Medical Research publishes translational and clinical research of international interest across all medical disciplines, enabling clinicians and other researchers to learn about developments and innovations within these disciplines and across the boundaries between disciplines. The journal publishes high quality research and reviews and aims to ensure that the results of all well-conducted research are published, regardless of their outcome.