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MLP调控MDVs介导肺癌放疗后炎症

中文摘要英文摘要

目的:肺癌放射性治疗所诱发的肺炎是放疗常见并发症,但是机制仍不明确,亟待研究。方法:通过基因编辑技术构建了ATMLP过表达及敲低细胞系,并使用Western Blot、免疫荧光、Transwell共培养等技术探究线粒体衍生囊泡(MDVs)介导放疗诱发炎症中的作用以及ATMLP、DRP-1和PGAM5对MDVs的影响。结果:电离辐射促进了ATMLP及其介导的MDVs的表达。ATMLP表达的上调可导致PGAM5水平升高,并激活DRP-1的Ser616位点磷酸化。MDVs数量的增加则进一步促进了巨噬细胞向M1型表型的极化。结论:电离辐射可以导致细胞ATMLP表达水平升高,ATMLP的升高则可以通过PGAM5/DRP-1轴促使MDVs数量增加,导致巨噬细胞进行M1型极化,促进炎症发生。

OBJECTIVE: Pneumonia is induced after radiotherapy for lung cancer is a common complication of radiotherapy, but the mechanism remains unclear and needs to be studied urgently. METHODS: ATMLP overexpression and knockdown cell lines were constructed by gene editing techniques, and Western Blot, immunofluorescence, and Transwell co-culture were used to investigate the role of MDVs in inflammation induced by radiotherapy for pneumonia, and the effects of ATMLP, DRP-1, and PGAM5 on MDVs. RESULTS: Ionizing radiation promoted the expression of ATMLP as well as MDVs. Increased expression of ATMLP led to up-regulation of PGAM5 expression as well as pDRP-1 (ser616).Mechanistic of ATMLP Regulation of Mitochondrial-Derived Vesicle Mediated Radiotherapy Induced Pulmonary Inflammation in Lung CancerIncreased number of MDVs led to increased levels of macrophage M1-type polarization. CONCLUSION: Ionizing radiation can lead to an increase in the cellular ATMLP expression level, and the increase in ATMLP can contribute to the increase in the number of MDVs through the PGAM5/DRP-1 axis, leading to M1-type polarization of macrophages and promoting inflammation.

张爱悦、郑泽轩、周光明、裴海龙、鲁杰

苏州大学苏州医学院放射医学与防护学院,苏州,215127苏州大学苏州医学院放射医学与防护学院,苏州,215127苏州大学苏州医学院放射医学与防护学院,苏州,215127苏州大学苏州医学院放射医学与防护学院,苏州,215127苏州大学苏州医学院放射医学与防护学院,苏州,215127

肿瘤学基础医学医学研究方法

放射医学MLPMDVsRP-1PGAM5线粒体稳态

RadiologyATMLPMDVsDRP-1PGAM5Mitochondrial homeostasis.?????

张爱悦,郑泽轩,周光明,裴海龙,鲁杰.MLP调控MDVs介导肺癌放疗后炎症[EB/OL].(2025-04-25)[2025-04-28].http://www.paper.edu.cn/releasepaper/content/202504-218.点此复制

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