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

IF 2.9 4区 医学 Q1 Medicine
Xin Li, Lei Zhang, Guixiang Chen
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引用次数: 0

摘要

铁氧化在急性肾损伤(AKI)中的作用尚未完全揭示。我们的目的是探索 SNHG11/miR-324-3p 通过调节 GPX4 在 AKI 中调节铁氧化的新作用。为了在体内模拟 AKI,我们给 6 周大的雄性 C57BL/6 小鼠注射了脂多糖(LPS),并注射了 shRNA(sh-NC 或 sh-SNHG11)、miRNA antagomir(antagomir-NC 或 miR-324-3p antagomir)、miRNA agomir(agomir-NC 和 miR-324-3p agomir)来分别调控 SNHG11 和 miR-324-3p。为了刺激体外 AKI 模型,HK-2 细胞先与 LPS 培养 6 小时,然后分别转染 shRNA(sh-NC 或 sh-SNHG11)、miRNA mimics(mimics-NC 或 miR-324-3p mimics)、miRNA 抑制剂(inhibitor-NC 和 miR-324-3p inhibitor)。miR-324-3p mimics 和 SNHG11-wt 共转染会降低荧光素酶的相对活性,表明 miR-324-3p 是 SNHG11 的靶标。SNHG11 沉默增加了 LPS 刺激的 HK-2 细胞中 miR-324-3p 的表达。在 AKI 模型中,SNHG11 沉默和 miR-324-3p 上调都会加重 LPS 诱导的铁变态反应和肾损伤,并减少 GPX4,而 miR-324-3p 下调则会抑制 LPS 引起的损伤,并增加 GPX4。在 SNHG11 沉默的 AKI 模型中,miR-324-3p 的上调进一步增强了铁变态反应和肾损伤,并导致 GPX4 的表达降低。SNHG11 的减少导致肾小管上皮细胞中 miR-324-3p 的上调,从而导致 GPX4 的减少,引发 AKI 中的铁蛋白沉积。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
CiteScore
4.30
自引率
17.20%
发文量
145
审稿时长
2.3 months
期刊介绍: Information not localized
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