circUQCRC2通过靶向miR-381-3p激活血管内皮生长因子/NF-κB通路,促进儿童哮喘进展

Li‐Juan Yang, Shu‐Xiang Sui, Qing‐Hua Zheng, Min Wang
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引用次数: 0

摘要

本研究旨在探讨 circUQCRC2 在儿童哮喘中的作用和机制。通过建立卵清蛋白诱导的哮喘小鼠模型,从氧化应激、炎症和胶原沉积等方面评估circUQCRC2对儿童哮喘的影响。研究评估了 circUQCRC2 对血小板衍生生长因子-BB(PDGF-BB)诱导的平滑肌细胞(SMCs)的影响,预测和验证了 miRNA 下游 mRNA 及其相关通路,并评估了它们对哮喘小鼠的影响。消耗 circUQCRC2 可减轻哮喘小鼠的组织损伤,改善哮喘小鼠和 PDGF-BB 处理的 SMC 的炎症水平和氧化应激,抑制 SMC 的恶性增殖和迁移,改善气道重塑。从机制上讲,circUQCRC2通过miR-381-3p调控VEGFA的表达并激活NF-κB级联。促进 circUQCRC2 通过激活 miR-381-3p/VEGFA/NF-κB 级联刺激哮喘的发展。因此,敲除 circUQCRC2 或过表达 miR-381-3p 为治疗儿童哮喘提供了一种新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
circUQCRC2 promotes asthma progression in children by activating the VEGFA/NF‐κB pathway by targeting miR‐381‐3p
This study targeted to explore circUQCRC2's role and mechanism in childhood asthma. A mouse model of ovalbumin‐induced asthma was established to evaluate the effects of circUQCRC2 on childhood asthma in terms of oxidative stress, inflammation, and collagen deposition. The effects of circUQCRC2 on platelet‐derived growth factor‐BB (PDGF‐BB)‐induced smooth muscle cells (SMCs) were evaluated, the downstream mRNA of miRNA and its associated pathways were predicted and validated, and their effects on asthmatic mice were evaluated. circUQCRC2 levels were upregulated in bronchoalveolar lavage fluid of asthmatic mice and PDGF‐BB‐treated SMCs. Depleting circUQCRC2 alleviated tissue damage in asthmatic mice, improved inflammatory levels and oxidative stress in asthmatic mice and PDGF‐BB‐treated SMC, inhibited malignant proliferation and migration of SMCs, and improved airway remodeling. Mechanistically, circUQCRC2 regulated VEGFA expression through miR‐381‐3p and activated the NF‐κB cascade. circUQCRC2 knockdown inactivated the NF‐κB cascade by modulating the miR‐381‐3p/VEGFA axis. Promoting circUQCRC2 stimulates asthma development by activating the miR‐381‐3p/VEGFA/NF‐κB cascade. Therefore, knocking down circUQCRC2 or overexpressing miR‐381‐3p offers a new approach to treating childhood asthma.
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