miR-141-3p 通过 Keap1/Nrf2/ARE 信号通路减轻炎症和氧化应激诱导的 ARDS 肺纤维化

IF 3.3 4区 医学 Q3 IMMUNOLOGY
Immunologic Research Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI:10.1007/s12026-024-09503-7
Guangwen Long, Qian Zhang, Xiulin Yang, Hongpeng Sun, Chunling Ji
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引用次数: 0

摘要

本研究旨在探讨microRNA(miR)-141-3p对急性呼吸窘迫综合征(ARDS)肺纤维化的影响和机制。通过气管内滴加 10 毫克/千克脂多糖(LPS)建立大鼠 ARDS 模型,采用 RT-qPCR 法检测 miR-141-3p 和 Kelch 样 ECH 相关蛋白 1(Keap1)的表达。支气管肺泡灌洗液(BALF)和肺组织中的炎症因子用酶联免疫吸附试验(ELISA)测定。使用马森三色染色法和羟脯氨酸检测试剂盒对肺纤维化进行评估。组织氧化应激标记物水平由商用试剂盒进行评估。通过Western印迹分析研究了EMT通路和Keap1/核因子-红细胞2相关因子2(Nrf2)/抗氧化反应元件(ARE)通路的蛋白质变化。通过双荧光素酶报告实验验证了靶向关系。在 LPS 诱导的 ARDS 大鼠中,miR-141-3p 的表达明显上调,而 Keap1 则下调。在 LPS 诱导的 ARDS 大鼠中,miR-141-3p 的过表达降低了肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平,同时升高了丙二醛(MDA)的表达。在 LPS 诱导的 ARDS 大鼠体内,miR-141-3p 的升高降低了纤维化评分,增强了 E-cadherin 蛋白表达,降低了波形蛋白和 α-SMA 蛋白表达。miR-141-3p 的升高还上调了 Nrf2、血红素加氧酶-1(HO-1)和 NAD(P)H:quinone 氧化还原酶-1(NQO1)蛋白的水平。此外,Keap1的过表达逆转了miR-141-3p对LPS诱发的炎症、氧化应激和纤维化的抑制作用。 miR-141-3p可能通过Keap1/Nrf2/ARE信号通路减轻炎症和氧化应激诱发的ARDS肺纤维化。我们的研究为治疗 ARDS 提供了新思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

miR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway.

miR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway.

The present research aimed to investigate the effects and mechanisms of microRNA (miR)-141-3p on pulmonary fibrosis of acute respiratory distress syndrome (ARDS). A rat ARDS model was established by the intratracheal drip of 10 mg/kg lipopolysaccharide (LPS). miR-141-3p and Kelch-like ECH-associated protein 1 (Keap1) expression was detected using RT-qPCR assay. Inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissues were measured with enzyme-linked immunosorbent assay (ELISA). Lung fibrosis was evaluated using Masson's trichrome staining and hydroxyproline assay kits. Tissue oxidative stress marker levels were assessed by a commercial kit. Protein variations in the EMT pathway and Keap1/nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway were investigated by Western blot analysis. Targeting relationship verified by dual-luciferase reporter assay. The expression of miR-141-3p was significantly upregulated in LPS-induced ARDS rats, while Keap1 was downregulated. Overexpression of miR-141-3p decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, superoxide dismutase (SOD), and glutathione (GSH) while elevating malondialdehyde (MDA) expression in LPS-induced ARDS rats. Elevation of miR-141-3p reduced fibrosis scores, enhanced E-cadherin protein expression, and decreased vimentin and α-SMA protein expression in LPS-induced ARDS rats. This elevation of miR-141-3p also upregulated Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxido-reductase-1 (NQO1) proteins levels. Moreover, Keap1 overexpression reversed the inhibitory effects of miR-141-3p on LPS-triggered inflammation, oxidative stress, and fibrosis. miR-141-3p may attenuate inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway. Our study provides new ideas for the treatment of ARDS.

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来源期刊
Immunologic Research
Immunologic Research 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
83
审稿时长
6-12 weeks
期刊介绍: IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.
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