Zihe Zheng , Wei Wang , Ming Huang , Bo Chen , Tao Wang , Zheng Xu , Xin Jiang , Xiaofu Dai
{"title":"LYVE1 and IL1RL1 are mitochondrial permeability transition-driven necrosis-related genes in heart failure","authors":"Zihe Zheng , Wei Wang , Ming Huang , Bo Chen , Tao Wang , Zheng Xu , Xin Jiang , Xiaofu Dai","doi":"10.1016/j.biocel.2025.106738","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways.</div></div><div><h3>Methods</h3><div>We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC<img>1 assays were performed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Forty-six differentially expressed genes, and 3439 module genes were identified. <em>LYVE1</em>, <em>IL1RL1</em>, and <em>SERPINA3</em> were identified as significantly downregulated key genes, with <em>IL1RL1</em> and <em>SERPINA3</em> associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only <em>LYVE1</em> and <em>IL1RL1</em> were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells.</div></div><div><h3>Conclusions</h3><div><em>LYVE1</em> and <em>IL1RL1</em> were validated as key genes linked to mitochondrial permeability transition-driven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106738"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biochemistry & Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1357272525000056","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways.
Methods
We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC1 assays were performed in vitro.
Results
Forty-six differentially expressed genes, and 3439 module genes were identified. LYVE1, IL1RL1, and SERPINA3 were identified as significantly downregulated key genes, with IL1RL1 and SERPINA3 associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only LYVE1 and IL1RL1 were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells.
Conclusions
LYVE1 and IL1RL1 were validated as key genes linked to mitochondrial permeability transition-driven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.
期刊介绍：
IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research.
Topics of interest include, but are not limited to:
-Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism
-Novel insights into disease pathogenesis
-Nanotechnology with implication to biological and medical processes
-Genomics and bioinformatics
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
