Alterations in apoptotic pathways and expression of miR-134, miR-181, and miR-497 induced by Wharton’s jelly-derived mesenchymal stem cells in a rat model of ischemic brain injury

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-04-28 DOI:10.1016/j.ibneur.2025.04.015

Tahereh Alizamir , Ali Fathi Jouzdani , Fatemeh Attari , Leila Arab , Zeinab Ashaari , Alireza Komaki , Gholamreza Hassanzadeh

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Abstract

Background

MicroRNAs (miRNAs) play crucial roles in regulating cell survival and signaling pathways. Mesenchymal stem cells (MSCs), particularly those derived from Wharton’s Jelly (WJ-MSCs), have shown potential in promoting cell survival and reducing apoptosis. This study evaluates the effects of WJ-MSCs on miRNA expression and apoptosis markers in an ischemic brain injury model.

Methods

Male Wistar rats (n = 30) were divided into control, sham, WJ-MSCs, Middle Cerebral Artery Occlusion (MCAO), and MCAO+WJ-MSCs groups. After 60 minutes of ischemia and 24 hours of reperfusion, WJ-MSCs were administered intracerebroventricularly. Post-surgical brain samples were analyzed using immunohistochemistry, TUNEL assay, and qRT-PCR to measure Bax/Bcl-2 ratios and miRNA (miR-497, miR-134, miR-181) expression in the cortex.

Results

Immunohistochemistry revealed that the Bax/Bcl-2 ratio was significantly increased in the MCAO group, reflecting a pro-apoptotic state. In contrast, WJ-MSC treatment significantly reduced the Bax/Bcl-2 ratio in the ischemic cortex, suggesting a shift towards anti-apoptotic activity. Additionally, analysis of miRNA expression showed significantly elevated levels of miR-497, miR-134, and miR-181 in the brains of ischemic rats, which were associated with increased neuronal cell death. WJ-MSC treatment effectively modulated these miRNAs, resulting in a marked reduction in their expression. Furthermore, the TUNEL assay confirmed a substantial reduction in the number of apoptotic cells in the MCAO+WJ-MSCs group compared to the MCAO group. In the cortex, apoptotic cells were observed in WJ-MSC-treated rats, indicating enhanced neuronal survival.

Conclusion

WJ-MSCs mitigate ischemic brain injury by modulating miRNA expression and apoptotic markers, promoting neuronal survival. These findings highlight their potential as a therapeutic strategy for ischemic brain injuries.

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沃顿果冻源间充质干细胞诱导大鼠缺血性脑损伤模型中miR-134、miR-181和miR-497凋亡通路和表达的改变

micrornas （miRNAs）在调节细胞存活和信号通路中起着至关重要的作用。间充质干细胞（MSCs），特别是来源于沃顿水母的间充质干细胞（WJ-MSCs），在促进细胞存活和减少细胞凋亡方面具有潜在的作用。本研究评估了WJ-MSCs对缺血性脑损伤模型中miRNA表达和凋亡标志物的影响。方法将30只雄性Wistar大鼠（n = ）分为对照组、假手术组、WJ-MSCs组、大脑中动脉闭塞组和MCAO+WJ-MSCs组。缺血60 分钟，再灌注24 小时后，将WJ-MSCs注入脑室。采用免疫组织化学、TUNEL和qRT-PCR对术后脑样本进行分析，测量Bax/Bcl-2比率和皮层中miRNA （miR-497、miR-134、miR-181）的表达。结果免疫组化结果显示，MCAO组细胞Bax/Bcl-2比值明显升高，呈促凋亡状态。相比之下，WJ-MSC治疗显著降低了缺血皮质中Bax/Bcl-2的比例，表明其向抗凋亡活性的转变。此外，miRNA表达分析显示，缺血大鼠大脑中miR-497、miR-134和miR-181水平显著升高，这与神经元细胞死亡增加有关。WJ-MSC治疗有效地调节了这些mirna，导致它们的表达显著降低。此外，TUNEL实验证实，与MCAO组相比，MCAO+WJ-MSCs组的凋亡细胞数量大幅减少。wj - msc处理的大鼠皮层出现凋亡细胞，表明神经元存活增强。结论wj - mscs通过调节miRNA表达和凋亡标志物，促进神经元存活，减轻缺血性脑损伤。这些发现突出了它们作为缺血性脑损伤治疗策略的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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