eNAMPT 是人类和小鼠肺纤维化中的新型DAMP和治疗标
Nancy G Casanova1, Jose D Herazo-Maya2, Carrie L Kempf3
1University of Florida, Jupiter, Florida, United States.
American journal of respiratory cell and molecular biology
|March 24, 2025
概括
细胞外尼古丁胺酸转移酶 (eNAMPT) 在异常性肺纤维化 (IPF) 中升高,导致疾病的严重程度. 通过ALT-100抗体中和eNAMPT,可以通过减少肺纤维化和炎症来治疗IPF.
科学领域:
- 肺部病理学 肺部病理学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 异形性肺纤维化 (IPF) 是一种致命的无治肺部疾病,突出显示需要新的治疗方法.
- 细胞外尼古丁胺酸基转移酶 (eNAMPT) 是一种与损伤相关的分子模式蛋白和通关式受体4 (TLR4) 配体,与纤维性疾病有关.
- eNAMPT有助于肺部和肝脏纤维化严重程度.
研究的目的:
- 研究细胞外尼古丁胺胺酸基转移酶 (eNAMPT) 作为异常性肺纤维化 (IPF) 的治疗标.
- 在IPF的临床前模型中评估ENAMPT中和单克隆抗体 (mAb) ALT-100的疗效.
主要方法:
- 来自IPF患者的血液,PBMC和肺组织以及白素诱导的肺纤维化小鼠模型的分析.
- 生物化学,组织学和基因表达分析,包括批量和单细胞RNA测序.
- 在临床前模型中对ALT-100 mAb治疗的评估.
主要成果:
- 在IPF患者中增加NAMPT表达与疾病严重程度和生存率降低相关.
- 在小鼠中,白胺诱导的肺纤维化显示炎症增加,肺硬化和TGFβ通路激活,所有这些都被ALT-100 mAb缓解.
- 单细胞RNA测序揭示ALT-100 mAb逆转了白血素诱导的2型膜细胞扩张和细胞到介质酶转变.
结论:
- eNAMPT/TLR4信号通路从根本上参与了肺纤维化.
- 使用ALT-100 mAb中和eNAMPT代表了IPF的可行的治疗策略.
- 针对eNAMPT解决了对新型IPF治疗的关键未满足需求.
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