氧浓度变化对人肺动脉内皮细胞中ANGPTL8表达的影响

doi:10.16352/j.issn.1001-6325.2025.01.0012

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (1): 12-19.doi: 10.16352/j.issn.1001-6325.2025.01.0012

氧浓度变化对人肺动脉内皮细胞中ANGPTL8表达的影响

张宗丽^1,2, 李涛^1,2,4, 马菁文³, 张嘉鑫¹, 李兴朝², 席世兵^1,2,4*

十堰市太和医院(湖北医药学院附属医院)1.儿童疾病研究所; 2.儿科2病区,湖北十堰 442000;
湖北医药学院 3.药学院; 4.儿童疾病研究所, 湖北十堰 442000

收稿日期:2024-04-17 修回日期:2024-07-15 出版日期:2025-01-05 发布日期:2024-12-25
通讯作者: ^*xishibing2009 @163.com
基金资助:
湖北省自然科学基金青年项目(2021CFB270);2022 年度湖北省教育厅项目(Q20222113);十堰市科技局引导性项目(21Y20)

Impact of oxygen concentration changes on ANGPTL8 expression of human pulmonary artery endothelial cells

ZHANG Zongli^1,2, LI Tao^1,2,4, MA Jingwen³, ZHANG Jiaxin¹, LI Xingchao², XI Shibing^1,2,4*

1. Institute of Pediatric Disease, 2. Department of Pediatrics, Taihe Hospital, Shiyan 442000;
3. School of Pharmaceutical Sciences; 4. Institute of Pediatric Disease, Hubei University of Medicine, Shiyan 442000, China

Received:2024-04-17 Revised:2024-07-15 Online:2025-01-05 Published:2024-12-25
Contact: ^*xishibing2009 @163.com

摘要/Abstract

摘要： 目的探讨氧浓度变化对肺动脉内皮细胞(HPAECs)中血管生成素样蛋白8(ANGPTL8)表达的影响,以及ANGPTL8在肺动脉高压(PH)中的作用和机制。方法低氧(1%)和高氧(85%)处理HPAECs, Western blot和PCR等检测ANGPTL8的表达,并分析内皮-间质转化(EndMT)及ERK信号通路的变化。同时,高氧处理新生大鼠,构建支气管肺发育不良(BPD)模型,观察肺组织中ANGPTL8蛋白表达及ERK信号通路的变化。结果低氧组HPAECs中ANGPTL8的蛋白表达显著升高,伴随ERK信号通路的抑制(P＜0.05)。ANGPTL8促进低氧诱导的EndMT过程(P＜0.05),沉默ANGPTL8可以部分逆转EndMT过程。高氧组HPAECs和大鼠肺组织中ANGPTL8蛋白表达降低,伴随ERK信号通路的激活(P＜0.05)。结论 HPAECs中ANGPTL8对氧浓度变化高度敏感,其表达的变化与ERK信号通路的活性状态密切相关,对PH的发展具有潜在的调控作用。

关键词: 肺动脉高压, 血管生成素样蛋白8(ANGPTL8), 内皮-间质转化(EndMT), 低氧, 高氧

Abstract: Objective To explore the impact of change in oxygen concentration on the expression of angiopoietin-like protein 8 (ANGPTL8) by endothelial cells (HPAECs) of human pulmonary artery, and the role and mechanism of ANGPTL8 in pulmonary hypertension (PH). Methods HPAECs were treated under hypoxic and hyperoxic conditions, and the expression level of ANGPTL8 was detected using Western blot and PCR. The changes in endothelial-mesenchymal transition (EndMT) and ERK signaling pathway activity were analyzed. Simultaneously, newborn rats were exposed to hyperoxia to develop a bronchopulmonary dysplasia (BPD) model. The expression of ANGPTL8 protein and changes in the ERK signaling pathway in lung tissue were observed. Results Under hypoxic condition, the protein expression of ANGPTL8 in HPAECs was significantly increased accompanied by inhibition of the ERK signaling pathway. ANGPTL8 promoted the EndMT process induced by hypoxia(P＜0.05) and silencing the expression of ANGPTL8 resulted in a partial reversal of EndMT. The protein expression of ANGPTL8 was decreased in hyperoxia-exposed HPAECs and rat lung tissues accompanied by the activation of the ERK signaling pathway(P＜0.05). Conclusions ANGPTL8 is highly sensitive to the change of oxygen concentration in HPAECs and closely correlated to its expression level and to the activity of ERK signaling pathway. This result suggests that ANGPTL8 may have potential regulatory effects on the development of PH.

Key words: pulmonary hypertension, angiopoietin-like protein 8 (ANGPTL8), endothelial-mesenchymal transition (EndMT), hypoxia, hyperoxia

中图分类号:

张宗丽, 李涛, 马菁文, 张嘉鑫, 李兴朝, 席世兵. 氧浓度变化对人肺动脉内皮细胞中ANGPTL8表达的影响[J]. 基础医学与临床, 2025, 45(1): 12-19.

ZHANG Zongli, LI Tao, MA Jingwen, ZHANG Jiaxin, LI Xingchao, XI Shibing. Impact of oxygen concentration changes on ANGPTL8 expression of human pulmonary artery endothelial cells[J]. Basic & Clinical Medicine, 2025, 45(1): 12-19.

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氧浓度变化对人肺动脉内皮细胞中ANGPTL8表达的影响

Impact of oxygen concentration changes on ANGPTL8 expression of human pulmonary artery endothelial cells

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