促红细胞生成素通过激活 FGF23/FGFR4/ERK 信号通路减轻肺缺血再灌注损伤。
Erythropoietin alleviates lung ischemia-reperfusion injury by activating the FGF23/FGFR4/ERK signaling pathway.
机构信息
Pulmonary and Critical Care Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Department of Neonatology, Hangzhou Children's Hospital, Hangzhou, China.
出版信息
PeerJ. 2024 Mar 27;12:e17123. doi: 10.7717/peerj.17123. eCollection 2024.
BACKGROUND
The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI).
METHODS
Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model and , respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study.
RESULTS
It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model and than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher.
CONCLUSION
EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.
背景
本研究旨在探讨促红细胞生成素（EPO）对肺缺血再灌注损伤（LIRI）的影响。
方法
采用 Sprague Dawley 大鼠和 BEAS-2B 细胞分别构建缺血再灌注（I/R）诱导模型和 tert-butyl hydroperoxide（TBHP）诱导细胞损伤模型，随后用不同浓度的 EPO 处理 I/R 大鼠和 TBHP 诱导的细胞。此外，本研究还纳入了 40 例 LIRI 患者和健康对照者。
结果
与对照组相比，LIRI 模型和细胞损伤模型中的肺组织损伤、细胞凋亡以及 BAX 和 caspase-3 的表达水平更高，而 Bcl-2、FGF23 和 FGFR4 的表达水平更低。EPO 给药可显著减轻肺组织损伤和细胞凋亡，并上调 FGF23 和 FGFR4 的表达。此外，EPO 还通过 FGF23/FGFR4/p-ERK1/2 信号通路发挥保护作用。值得注意的是，与健康对照组相比，LIRI 患者的血清 EPO、FGF23、FGFR4 和 Bcl-2 表达水平降低，而 caspase-3 和 BAX 的表达水平升高。
结论
EPO 可有效改善 LIRI，这可能与激活 FGF23/FGFR4/p-ERK1/2 信号通路有关。
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