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在纤维化中准AXL细胞网络

Sturla M Grøndal¹, Magnus Blø², Linn I H Nilsson²

¹Department of Biomedicine, University of Bergen, Bergen, Norway.

Frontiers in immunology

|November 19, 2024

概括

在小鼠模型中,使用贝姆森丁尼布准AXL激酶可以减少纤维化. 这种方法抑制了免疫细胞的透和介质细胞的增殖,支持AXL抑制剂治疗慢性病 (CKD).

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
分子生物学分子生物学
在瘤学瘤学.

背景情况:

慢性病 (CKD) 的发病率正在全球上升,与肥胖和糖尿病有关.
AXL受体氨酸激酶与CKD的发病有关,使其成为治疗点.

研究的目的:

调查AXL抑制在缓解纤维化的有效性.
在临床前CKD模型中阐明AXL抑制的分子机制.

主要方法:

利用脏损伤的小鼠单边尿路阻塞 (UUO) 模型.
在疾病进展过程中预防性地使用选择性AXL激酶抑制剂贝门替尼布.
在早期和晚期的时间点使用质量细胞测量分析脏组织,以分析细胞群.

主要成果:

在UUO模型中,预防性贝姆森提尼布治疗显著减轻了纤维化.
抑制AXL降低了间细胞数量和先天免疫细胞透.
在受AXL抑制的脏中观察到上皮细胞的比例增加.
鉴定了AXL表达在介质细胞,细胞周细胞,巨细胞和树突细胞中.

结论:

AXL向破坏了一个关键的细胞网络,导致CKD中纤维化进展.
这些发现为治疗CKD的AXL抑制剂的临床开发提供了强有力的理由.

关键词:

在 Axl Axl 轴上单边尿路阻塞 (UUO) 是一种单边的尿路阻塞.贝姆森提尼布 (Bemcentinib) 是一种药物.纤维化纤维化这是一种炎症炎症炎症炎症.质量细胞计 (CyTOF) 是一种质量细胞计.

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