Zhang Ziqing, Ma Jinmiao, Shi Minyu, Huang Jingcong, Xu Zhenyu
Department of Emergency Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong, Shanghai, 200137, China.
BMC Nephrol. 2025 Apr 21;26(1):201. doi: 10.1186/s12882-025-04123-1.
Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a crucial anti-apoptotic protein; however, its role and associated molecular pathways in ferroptosis remain largely unexplored. This study aimed to investigate the effects of CIAPIN1 on ferroptosis in lipopolysaccharide (LPS)-induced podocytes and the associated underlying phenomenon.
In this study, we recruited 50 sepsis patients (aged 56.63 ± 10.33) with acute kidney injury (AKI), 50 sepsis patients without AKI, and 50 healthy controls. We established an in vitro model of LPS-induced MPC5 podocytes. RT-qPCR and Western blotting were used to evaluate mRNA and protein expression, respectively.
Serum CIAPIN1 is downregulated in patients with septic AKI and LPS-induced podocytes. CIAPIN1 overexpression (OE-CIAPIN1) attenuated cell proliferation and apoptosis in LPS-induced podocytes. OE-CIAPIN1 elevated phosphorylated phosphoinositide 3-kinase (p-PI3K; p85, Tyr458) and phosphorylated protein kinase B (p-Akt; Ser473) levels in LPS-induced podocytes. OE-CIAPIN1 significantly elevated synaptopodin mRNA levels and remarkably lowered desmin mRNA expression in MPC5 cells. In contrast, treatment with the PI3K/Akt pathway inhibitor, LY294002, reversed synaptopodin and desmin mRNA expression in MPC5 cells. Additionally, OE-CIAPIN1 reduced the malondialdehyde (MDA) content and Fe2 + concentration in the lysate of MPC5 cells, while elevating the MDA content and Fe2 + concentration by LY294002 treatment. Furthermore, OE-CIAPIN1 increased ferroptosis-related proteins, including solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in MPC5 cells, which was reversed by LY294002 treatment.
These results suggest that serum CIAPIN1 inhibits LPS-induced ferroptosis in podocytes by regulating the PI3K/AKT signaling pathway.
细胞因子诱导的凋亡抑制因子1（CIAPIN1）是一种关键的抗凋亡蛋白；然而，其在铁死亡中的作用及相关分子途径在很大程度上仍未被探索。本研究旨在探讨CIAPIN1对脂多糖（LPS）诱导的足细胞铁死亡的影响及相关潜在机制。
本研究纳入了50例患有急性肾损伤（AKI）的脓毒症患者（年龄56.63±10.33岁）、50例无AKI的脓毒症患者以及50例健康对照。我们建立了LPS诱导的MPC5足细胞体外模型。分别采用RT-qPCR和蛋白质免疫印迹法评估mRNA和蛋白质表达。
脓毒症AKI患者及LPS诱导的足细胞中血清CIAPIN1下调。CIAPIN1过表达（OE-CIAPIN1）减轻了LPS诱导的足细胞的细胞增殖和凋亡。OE-CIAPIN1提高了LPS诱导的足细胞中磷酸化磷脂酰肌醇3激酶（p-PI3K；p85，Tyr458）和磷酸化蛋白激酶B（p-Akt；Ser473）的水平。OE-CIAPIN1显著提高了MPC5细胞中突触素蛋白mRNA水平，并显著降低了结蛋白mRNA表达。相反，用PI3K/Akt途径抑制剂LY294002处理可逆转MPC5细胞中突触素蛋白和结蛋白mRNA表达。此外，OE-CIAPIN1降低了MPC5细胞裂解物中的丙二醛（MDA）含量和Fe2+浓度，而LY294002处理则提高了MDA含量和Fe2+浓度。此外，OE-CIAPIN1增加了MPC5细胞中与铁死亡相关的蛋白质，包括溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4），LY294002处理可逆转这一现象。
这些结果表明，血清CIAPIN1通过调节PI3K/AKT信号通路抑制LPS诱导的足细胞铁死亡。
