PTEN的敲除抑制自噬依赖性铁下垂，以减轻LPS诱导的脓毒症相关的急性肾损伤
Knockdown of PTEN Inhibits Autophagy-Dependent Ferroptosis to Alleviate LPS-Induced Sepsis-Associated Acute Kidney Injury.
摘要(中文译文)
本研究旨在探讨PTEN调控脓毒症相关急性肾损伤（SA-AKI）中自噬依赖性铁死亡的机制。利用GSE65682数据集进行生物信息学分析，筛选与自噬依赖性铁死亡相关的基因。采用qRT-PCR验证关键基因的表达。通过Cell Counting Kit-8和集落形成实验测定细胞增殖。采用流式细胞术检测细胞凋亡、线粒体膜电位、Fe2+和ROS水平。利用透射电子显微镜观察线粒体功能和自噬情况。通过Western blotting进行蛋白分析。为验证关键基因PTEN在SA-AKI中的作用，通过脂多糖（LPS）诱导建立SA-AKI体内模型。PTEN被鉴定为关键基因，研究结果显示其在SA-AKI中高表达。在LPS诱导的SA-AKI体外细胞模型中，PTEN敲低增强了细胞增殖，抑制了细胞凋亡，并降低了细胞内Fe2+和ROS水平（P < 0.05，P < 0.01）。此外，PTEN敲低减轻了LPS诱导的线粒体肿胀和自噬体积累，观察到的自噬结构减少。PTEN敲低上调了Nrf2、SLC7A11和GPX4的表达，导致COX2和4-HNE表达降低，并通过激活Nrf2/SLC7A11/GPX4信号通路调控自噬依赖性铁死亡。此外，PTEN敲低减轻了SA-AKI中LPS诱导的肾损伤，证明其对SA-AKI具有保护作用。值得注意的是，ML385抑制Nrf2可逆转PTEN敲低的保护作用。本研究阐明，PTEN敲低通过激活Nrf2/SLC7A11/GPX4信号通路调控SA-AKI中的自噬依赖性铁死亡。
Abstract
This research aims to explore the mechanism whereby PTEN modulates autophagy-dependent ferroptosis in sepsis-associated acute kidney injury (SA-AKI). Bioinformatics analysis was performed using the GSE65682 dataset to screen genes associated with autophagy-dependent ferroptosis. qRT-PCR was performed to validate the expression of key genes. Cell proliferation was determined via the Cell Counting Kit-8 and colony formation assays. Apoptosis, mitochondrial membrane potential, Fe2+ and ROS levels were measured via flow cytometry. Mitochondrial function and autophagy were observed using transmission electron microscopy. Protein analysis was conducted via Western blotting. To verify the role of the key gene PTEN in SA-AKI, an in vivo model of SA-AKI was established via lipopolysaccharide (LPS) induction. PTEN was identified as a key gene, with findings showing that it is highly expressed in SA-AKI. In the LPS-induced in vitro cell model of SA-AKI, PTEN knockdown enhanced cell proliferation, inhibited apoptosis, and reduced intracellular Fe2+ and ROS levels (P < 0.05, P < 0.01). Additionally, LPS-induced mitochondrial swelling and autophagosome accumulation were alleviated by PTEN knockdown, with fewer autophagic structures observed. PTEN knockdown upregulated the expression of Nrf2, SLC7A11, and GPX4, leading to reduced expression of COX2 and 4-HNE, and regulated autophagy-dependent ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway. Furthermore, PTEN knockdown mitigated LPS-induced renal injury in SA-AKI, demonstrating its protective effect against SA-AKI. Notably, Nrf2 inhibition by ML385 reversed the protective effects of PTEN knockdown. This study elucidates that the knockdown of PTEN activates the Nrf2/SLC7A11/GPX4 signaling pathway to modulate autophagy-dependent ferroptosis in SA-AKI.
如何引用
AMA
Dede Lian, Qingling Zhang, Hongjun Li. Knockdown of PTEN Inhibits Autophagy-Dependent Ferroptosis to Alleviate LPS-Induced Sepsis-Associated Acute Kidney Injury.. Inflammation. 2026; doi:10.1007/s10753-026-02529-z.
APA
Dede Lian, Qingling Zhang, Hongjun Li (2026). Knockdown of PTEN Inhibits Autophagy-Dependent Ferroptosis to Alleviate LPS-Induced Sepsis-Associated Acute Kidney Injury.. Inflammation. https://doi.org/10.1007/s10753-026-02529-z
GB/T 7714
Dede Lian, Qingling Zhang, Hongjun Li. Knockdown of PTEN Inhibits Autophagy-Dependent Ferroptosis to Alleviate LPS-Induced Sepsis-Associated Acute Kidney Injury.[J]. Inflammation, 2026 doi:10.1007/s10753-026-02529-z.
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