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微小RNA 135-5P与p62之间的潜在关联及其对多发性硬化症中NRF2信号通路的影响

The Potential Association Between microRNA 135-5P and p62 and Their Effect on NRF2 Pathway in Multiple Sclerosis.

作者信息

Abusree Ahmed Azza, Fayez Hasan Salwa, Ahmed Rashed Laila, Ragab Noura, Shehata Ismail Rania, Mostafa Gharib Doaa

机构信息

Medical Biochemistry and Molecular Biology Department, Unit of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Neurology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Rep Biochem Mol Biol. 2024 Jan;12(4):512-521. doi: 10.61186/rbmb.12.4.512.

Abstract

BACKGROUND

Multiple Sclerosis (MS) is a prevalent non-traumatic disabling disease affecting young adults, characterized by complexity in its pathogenesis. Nuclear factor erythroid 2-Related Factor 2 (NRF2) serves as a crucial transcriptional regulator of anti-inflammatory and antioxidant enzymes, influenced by the ubiquitous protein p62. It acts as a scaffold directing substrates to autophagosomes. This study aims to explore the potential association between microRNA 135-5p and p62 and their impact on inflammation and oxidative stress through the NRF2 pathway in MS.

METHODS

The study included 30 healthy controls and 60 MS patients (relapsing-remitting and secondary progressive). Real-time PCR was employed for the detection of Nrf2, p62, miRNA135-5P, and NF-κB in serum, while p53 levels were determined using ELISA.

RESULTS

Nrf2 and p62 expression was significantly downregulated in the MS group compared to controls. Conversely, miRNA135-5P, NF-κB expression, and P53 levels were significantly elevated in the MS group.

CONCLUSIONS

This study reveals a potential association between miRNA 135-5p and p62, indicating their role in the pathogenesis of MS. Results suggest that miRNA 135-5p and p62 may influence inflammation and oxidative stress in MS through the NRF2 pathway, potentially mediated by NF-κB and p53.

摘要

背景

多发性硬化症(MS)是一种影响年轻人的常见非创伤性致残疾病,其发病机制复杂。核因子红细胞2相关因子2(NRF2)是抗炎和抗氧化酶的关键转录调节因子,受普遍存在的蛋白质p62影响。它作为一种支架,将底物导向自噬体。本研究旨在探讨微小RNA 135-5p与p62之间的潜在关联,以及它们通过MS中的NRF2途径对炎症和氧化应激的影响。

方法

该研究纳入了30名健康对照者和60名MS患者(复发缓解型和继发进展型)。采用实时PCR检测血清中的Nrf2、p62、miRNA135-5P和NF-κB,同时使用ELISA测定p53水平。

结果

与对照组相比,MS组中Nrf2和p62的表达显著下调。相反,MS组中miRNA135-5P、NF-κB的表达和P53水平显著升高。

结论

本研究揭示了miRNA 135-5p与p62之间的潜在关联,表明它们在MS发病机制中的作用。结果表明,miRNA 135-5p和p62可能通过NRF2途径影响MS中的炎症和氧化应激,可能由NF-κB和p53介导。

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1
A review on the importance of miRNA-135 in human diseases.关于miRNA - 135在人类疾病中的重要性的综述。
Front Genet. 2022 Sep 6;13:973585. doi: 10.3389/fgene.2022.973585. eCollection 2022.
6
NF-κB signaling in inflammation and cancer.炎症与癌症中的核因子-κB信号传导
MedComm (2020). 2021 Dec 16;2(4):618-653. doi: 10.1002/mco2.104. eCollection 2021 Dec.

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