{"title":"Anti-atherosclerotic effects of LncRNA NEXN-AS1 by regulation of canonical inflammasome pathway of pyroptosis via NEXN.","authors":"Fei Chen, Yun-Yong Lin, Rui Chen, Wen-Jie Lu, Yi-Wen Wu, Shaodong Qiu, Limei Wu","doi":"10.5603/fhc.102206","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>lncRNA NEXN-AS1 could act as a target for maintaining endothelium homeostasis, increasing plaque stability, and delaying the progression of atherosclerosis.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"191-202"},"PeriodicalIF":1.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Folia histochemica et cytobiologica","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.5603/fhc.102206","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/13 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
Dongyu Zhang, Linn Abraham, Joshua Demb, Diana L Miglioretti, Shailesh Advani, Brian L Sprague, Louise M Henderson, Tracy Onega, Karen J Wernli, Louise C Walter, Karla Kerlikowske, John T Schousboe, Ellen S O'Meara, Dejana Braithwaite
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.