<br>外泌体 miR-126-3p：通过调节人脐静脉内皮细胞中的 SLC7A5/mTOR 信号通路来潜在保护血管损伤,Scandinavian Journal of Immunology

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外泌体 miR-126-3p：通过调节人脐静脉内皮细胞中的 SLC7A5/mTOR 信号通路来潜在保护血管损伤
Scandinavian Journal of Immunology ( IF 4.1 ) Pub Date : 2024-01-16 , DOI: 10.1111/sji.13354
Ke Zhu _{1,

2} , Chen Liu ₃ , Xiaofang Guo ₄ , Xuting Zhang ₄ , Jiaxin Xie ₂ , Songmiao Xie ₂ , Qing Qi ₅ , Bin Yang ₁

Affiliation

系统性硬化症（SSc）是一种慢性自身免疫性结缔组织疾病。血管损伤是SSc的重要特征之一，影响疾病的进展和预后。 MiR-126-3p是调节血管结构和功能的重要microRNA（miRNA），可以通过外泌体运输。然而，miR-126-3p 在 SSc 血管损伤中的作用仍不清楚。因此，我们重点关注miR-126-3p与SSc血管损伤之间的联系，并研究miR-126-3p在SSc血管损伤中的潜在作用。首先，这项研究成功地从临床血浆样本中提取了细胞外囊泡，并表征了其中的外泌体。然后，我们通过在线数据库预测并筛选了雷帕霉素的靶通路哺乳动物/机械靶标（mTOR）和miR-126-3p的靶基因SLC7A5。接下来，我们构建了 SSc 小鼠用于体内研究。结果显示，血浆外泌体中miR-126-3p的表达减少，而主动脉中SLC7A5的表达、自噬和脂质过氧化增加。荧光素酶报告基因检测表明 miR-126-3p 可以与 SLC7A5 结合，导致其表达减少。体外实验表明，外泌体 miR-126-3p 可以被人脐静脉内皮细胞（HUVEC）内化。 miR-126-3p组表现出增强的细胞活力和管形成能力，以及血管形成标记物CD31的表达增加。此外，miR-126-3p下调HUVEC中SLC7A5和LC3的蛋白表达，同时上调mTOR、P62、PPARγ和CPT-1的蛋白表达。然而，miR-126-3p 对 HUVEC 的影响被 mTOR 抑制剂抵消，并被 mTOR 激活剂增强。结果表明，外泌体 miR-126-3p 具有通过调节 HUVEC 中的 SLC7A5/mTOR 信号通路来防止 SSc 血管损伤的潜力。

"点击查看英文标题和摘要"

Exosomal miR-126-3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR-126-3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR-126-3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR-126-3p and vascular damage in SSc, as well as investigated the potential role of miR-126-3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR-126-3p through online databases. Next, we constructed SSc mice for in vivo studies. The results showed that the expression of miR-126-3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR-126-3p can bind to SLC7A5, resulting in a decrease in its expression. In vitro experiments have shown that exosomal miR-126-3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR-126-3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR-126-3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPARγ, and CPT-1. However, the effects of miR-126-3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR-126-3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.

更新日期：2024-01-16

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