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基于N-phenylquinazolin-4-amine的EGFR TKIs通过调节表皮细胞-巨细胞相互作用中的EGFR/ERBB3轴来抑制肺纤维化

Ji-Hee Kim¹, Seo-Hyun Choi¹, Jae-Kyung Nam¹

¹Division of Radiation Biomedical Research, Korea Institute of Radiologic and Medical Sciences, Seoul, Korea.

Communications biology

|December 1, 2025

概括

EGFR氨酸激酶抑制剂 (TKI) 在治疗肺纤维化 (PF) 中表现有前途. 针对肺细胞中的EGFR/ERBB3通路减少了纤维化和炎症,这表明PF的新治疗策略.

科学领域:

肺部医学肺部医学
在瘤学瘤学.
免疫学免疫学免疫学

背景情况:

皮表皮生长因子受体 (EGFR) 信号传递在肺纤维化 (PF) 中至关重要.
目前针对PF中的EGFR的治疗策略有限.
膜上皮细胞中的EGFR/ERBB3轴与PF的病原发生有关.

研究的目的:

在PF的临床前模型中评估基于N-phenylquinazolin-4-amine的EGFR氨酸激酶抑制剂 (TKI).
调查EGFR/ERBB3信号通路在PF期间免疫上皮相互作用中的作用.
为了比较达科米蒂尼布和宁泰达尼布在减弱PF的疗效.

主要方法:

利用白素和辐射诱导的肺纤维化病例的小鼠模型.
通过EGFR TKIs评估了膜上皮质EGFR/ERBB3轴的调制.
在人类膜上皮细胞中进行EGFR/ERBB3敲击.
分析了细胞因子表达 (TNF-α,IFN-γ,IL-6) 和化EGFR/ERBB3水平.
在IPF患者单细胞RNA-seq数据中检查了EGFR相关基因表达.

主要成果:

通过调节膜上皮细胞中的EGFR/ERBB3轴,EGFR TKIs减弱了纤维化.
在早期炎症期间,EGFR配体在膜巨细胞中被上调.
在上皮细胞中观察到持续的EGFR/ERBB3酸化.
抑制EGFR/ERBB3可以减少炎症性细胞因子的产生.
与Nintedanib相比,达科米提尼布显示出更强的TNF-α,IFN-γ和IL-6抑制.
在人类IPF组织和细胞中证实了高酸化EGFR/ERBB3和EGFR通路激活.

结论:

向免疫上皮层EGFR/ERBB3信号是一种有前途的抗纤维菌策略.
EGFR TKIs,特别是达科米替尼,显示出治疗肺纤维化的潜力.
这项研究强调了一个关键的反循环,涉及EGFR信号在PF进展.

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