Anti-atherosclerotic effects of LncRNA NEXN-AS1 by regulation of canonical inflammasome pathway of pyroptosis via NEXN.

IF 1.7 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Folia histochemica et cytobiologica Pub Date : 2024-01-01 Epub Date: 2025-01-13 DOI:10.5603/fhc.102206
Fei Chen, Yun-Yong Lin, Rui Chen, Wen-Jie Lu, Yi-Wen Wu, Shaodong Qiu, Limei Wu
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Abstract

Introduction: Pyroptosis is closely related to many chronic diseases including atherosclerosis, but the potential pathomechanisms are still unclear. This study was aimed at exploring how lncRNAs may contribute to pyroptosis and the potential mechanisms.

Material and methods: We performed in vitro assays to investigate the effects of a relatively newly discovered lncRNA, NEXN-AS1, on pyroptosis. Two types of vascular wall cells, i.e. human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), were used as cell models in this study. A previously constructed lentivirus vector was used to overexpress lncRNA NEXN-AS1 and a small interfering RNA (siRNA) mimic against NEXN to knockdown NEXN. The mRNA and protein levels of molecules of pyroptosis in the canonical inflammasome pathway, including nucleotide-binding oligomerisation segment-like receptor family 3 (NLRP3), caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were detected using quantitative real-time PCR and Western blot analysis, respectively.

Results: We found that lentivirus-mediated overexpression of lncRNA NEXN-AS1 increased the expression levels of NEXN and markedly reduced the expression of critical molecules involved in pyroptosis, including NLRP3, caspase-1, GSDMD, IL-1β, and IL-18, in both VSMCs and ECs. Furthermore, NEXN knockdown could reverse the effects of lncRNA NEXN-AS1 overexpression on pyroptosis.

Conclusions: lncRNA NEXN-AS1 could act as a target for maintaining endothelium homeostasis, increasing plaque stability, and delaying the progression of atherosclerosis.

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LncRNA NEXN- as1的抗动脉粥样硬化作用,通过NEXN调节焦亡的典型炎性体途径。
简介:.热蛋白沉积与包括动脉粥样硬化在内的多种慢性疾病密切相关,但其潜在的病理机制尚不清楚。本研究旨在探索 lncRNA 如何导致热蛋白沉积及其潜在机制。我们通过体外实验研究了一种新发现的lncRNA--NEXN-AS1对热蛋白沉积的影响。本研究使用了两种血管壁细胞,即人血管平滑肌细胞(VSMC)和内皮细胞(EC)作为细胞模型。使用先前构建的慢病毒载体过表达 lncRNA NEXN-AS1,并使用针对 NEXN 的小干扰 RNA(siRNA)模拟物敲除 NEXN。利用定量实时荧光定量PCR和Western印迹分析法分别检测了炎症小体通路中热解分子的mRNA和蛋白水平,包括核苷酸结合寡聚化段样受体家族3(NLRP3)、caspase-1、gasdermin D(GSDMD)、白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)。我们观察到,慢病毒介导的 lncRNA NEXN-AS1 的过表达提高了 NEXN 的表达水平,并显著降低了 VSMCs 和 ECs 中 NLRP3、caspase-1、GSDMD、IL-1β 和 IL-18 等参与裂解的关键分子的表达。结论:lncRNA NEXN-AS1可作为维持血管内皮稳态、斑块稳定性和延缓动脉粥样硬化进展的靶点。
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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
期刊最新文献
Diagnostic utility of immunocytochemistry by using liquid-based cytology (LBC) slides. Immunocytochemical localization of nitric oxide synthase-containing neurons in the visual cortex of the Mongolian gerbil. Inhibition of IGF2BP1 attenuates the progression of endometriosis through PTBP1. Nephroprotective effect of Ginsenoside Rg1 in lipopolysaccharide-induced sepsis in mice through the SIRT1/NF-κB signaling. Digital morphology network for effective teaching of cytology, histology and histopathology for medical and biology curriculum. VM3.0 Erasmus+ project.
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