鉴定和验证白血病抑制因子作为缺血性急性肾损伤的保护因子。

Lemei Hu, Chen Jiao, Haiyu Gu, Zhigang Zhu, Ming Liang
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引用次数: 0

摘要

背景:缺血再灌注损伤(IRI)是急性肾损伤(AKI)的常见病理生理机制。目前迫切需要对其潜在机制进行更全面的分析:我们使用 RNA 序列数据集 GSE153625 研究了 IRI-AKI 小鼠与假小鼠肾脏组织的差异表达基因(DEGs)。我们使用 cytohubba 插件提供的 10 种算法和四个外部数据集(GSE192532、GSE52004、GSE98622 和 GSE185383)筛选枢纽基因。建立了不同再灌注时间的 IRI-AKI 小鼠模型,以验证枢纽基因在肾脏中的表达。在缺氧/再氧合(H/R)条件下体外培养HK-2细胞,通过转染si-LIF或补充LIF蛋白来探索LIF基因的功能:结果:与假手术组相比,我们在IRI组共筛选了1,540个DEGs,发现LIF中枢基因可能在IRI-AKI中发挥潜在作用。LIF在IRI-AKI小鼠的肾脏组织以及在H/R条件下生长的HK-2细胞中明显上调。敲除 LIF 会加重 H/R 条件下的细胞凋亡和氧化应激(OS)损伤。给予 LIF 蛋白可缓解 si-LIF 的影响,减轻细胞凋亡和氧化应激损伤:这些研究结果表明,在 IRI-AKI 的早期阶段,LIF 基因在调节细胞凋亡和 OS 方面起着重要作用。因此,以LIF为靶点可能是治疗IRI-AKI的一种有前景的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification and validation of leukemia inhibitory factor as a protective factor in ischemic acute kidney injury.

Background: Ischemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms.

Materials and methods: The RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene.

Results: We screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular apoptosis and OS.

Conclusion: These findings indicate an important role of the LIF gene in term of regulating apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.

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