{"title":"LncRNA 小核仁核糖核酸宿主基因 11 在急性肾损伤中通过 miR-324-3p/GPX4 轴调节肾小管上皮细胞的铁凋亡","authors":"Xin Li, Lei Zhang, Guixiang Chen","doi":"10.1166/jbn.2023.3701","DOIUrl":null,"url":null,"abstract":"Role of ferroptosis in acute kidney injury (AKI) is not fully uncovered. We aim to explore a novel role that SNHG11/miR-324-3p modulated ferroptosis in AKI via modulating GPX4. To mimic AKI in vivo, 6-week male C57BL/6 mice were administrated with lipopolysaccharide (LPS). shRNA (sh-NC or sh-SNHG11), miRNA antagomir (antagomir-NC or miR-324-3p antagomir), miRNA agomir (agomir-NC and miR-324-3p agomir) were injected in mice to regulate SNHG11 and miR-324-3p, respectively. To stimulate the in vitro model of AKI, HK-2 cells were incubated with LPS for 6 h, followed by the transfection with shRNA (sh-NC or sh-SNHG11), miRNA mimics (mimics-NC or miR-324-3p mimics), miRNA inhibitor (inhibitor-NC and miR-324-3p inhibitor), respectively. Co-transfection of miR-324-3p mimics and SNHG11-wt decreased the relative luciferase activity, suggesting miR-324-3p was the target of SNHG11. SNHG11 silence increased miR-324-3p expression in LPS-stimulated HK-2 cells. Both of SNHG11 silence and miR-324-3p upregulation aggravated LPS-induced ferroptosis and kidney injury, and decreased GPX4 whereas downregulation of miR-324-3p inhibited LPS-caused impairment, and increased GPX4 in AKI models. In AKI models with SNHG11 silence, upregulation of miR-324-3p further enhanced ferroptosis and kidney injury, and resulted in the lower expression of GPX4. Decreased SNHG11 caused miR-324-3p upregulation in renal tubular epithelial cells, which led to GPX4 reduction that trigger ferroptosis in AKI.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":"32 1","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"LncRNA Small Nucleolar RNA Host Gene 11 Modulates Ferroptosis in Renal Tubular Epithelial Cells via miR-324-3p/GPX4 Axis in Acute Kidney Injury\",\"authors\":\"Xin Li, Lei Zhang, Guixiang Chen\",\"doi\":\"10.1166/jbn.2023.3701\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Role of ferroptosis in acute kidney injury (AKI) is not fully uncovered. We aim to explore a novel role that SNHG11/miR-324-3p modulated ferroptosis in AKI via modulating GPX4. To mimic AKI in vivo, 6-week male C57BL/6 mice were administrated with lipopolysaccharide (LPS). shRNA (sh-NC or sh-SNHG11), miRNA antagomir (antagomir-NC or miR-324-3p antagomir), miRNA agomir (agomir-NC and miR-324-3p agomir) were injected in mice to regulate SNHG11 and miR-324-3p, respectively. To stimulate the in vitro model of AKI, HK-2 cells were incubated with LPS for 6 h, followed by the transfection with shRNA (sh-NC or sh-SNHG11), miRNA mimics (mimics-NC or miR-324-3p mimics), miRNA inhibitor (inhibitor-NC and miR-324-3p inhibitor), respectively. Co-transfection of miR-324-3p mimics and SNHG11-wt decreased the relative luciferase activity, suggesting miR-324-3p was the target of SNHG11. SNHG11 silence increased miR-324-3p expression in LPS-stimulated HK-2 cells. Both of SNHG11 silence and miR-324-3p upregulation aggravated LPS-induced ferroptosis and kidney injury, and decreased GPX4 whereas downregulation of miR-324-3p inhibited LPS-caused impairment, and increased GPX4 in AKI models. In AKI models with SNHG11 silence, upregulation of miR-324-3p further enhanced ferroptosis and kidney injury, and resulted in the lower expression of GPX4. Decreased SNHG11 caused miR-324-3p upregulation in renal tubular epithelial cells, which led to GPX4 reduction that trigger ferroptosis in AKI.\",\"PeriodicalId\":15260,\"journal\":{\"name\":\"Journal of biomedical nanotechnology\",\"volume\":\"32 1\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of biomedical nanotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1166/jbn.2023.3701\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biomedical nanotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1166/jbn.2023.3701","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
LncRNA Small Nucleolar RNA Host Gene 11 Modulates Ferroptosis in Renal Tubular Epithelial Cells via miR-324-3p/GPX4 Axis in Acute Kidney Injury
Role of ferroptosis in acute kidney injury (AKI) is not fully uncovered. We aim to explore a novel role that SNHG11/miR-324-3p modulated ferroptosis in AKI via modulating GPX4. To mimic AKI in vivo, 6-week male C57BL/6 mice were administrated with lipopolysaccharide (LPS). shRNA (sh-NC or sh-SNHG11), miRNA antagomir (antagomir-NC or miR-324-3p antagomir), miRNA agomir (agomir-NC and miR-324-3p agomir) were injected in mice to regulate SNHG11 and miR-324-3p, respectively. To stimulate the in vitro model of AKI, HK-2 cells were incubated with LPS for 6 h, followed by the transfection with shRNA (sh-NC or sh-SNHG11), miRNA mimics (mimics-NC or miR-324-3p mimics), miRNA inhibitor (inhibitor-NC and miR-324-3p inhibitor), respectively. Co-transfection of miR-324-3p mimics and SNHG11-wt decreased the relative luciferase activity, suggesting miR-324-3p was the target of SNHG11. SNHG11 silence increased miR-324-3p expression in LPS-stimulated HK-2 cells. Both of SNHG11 silence and miR-324-3p upregulation aggravated LPS-induced ferroptosis and kidney injury, and decreased GPX4 whereas downregulation of miR-324-3p inhibited LPS-caused impairment, and increased GPX4 in AKI models. In AKI models with SNHG11 silence, upregulation of miR-324-3p further enhanced ferroptosis and kidney injury, and resulted in the lower expression of GPX4. Decreased SNHG11 caused miR-324-3p upregulation in renal tubular epithelial cells, which led to GPX4 reduction that trigger ferroptosis in AKI.