德克-1在慢性病中具有致病作用,通过促进巨细胞透和过渡到肌纤维细胞
Lingling Shen1,2,3, Jingyi Li1,2,3, Anqi Zhang1,2,3
1Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310000, China.
International journal of biological sciences
|September 17, 2025
概括
德克-1在纤维化脏中升级调节,并通过促进巨细胞透和过渡来驱动慢性病的进展. 抑制Dectin-1显示出治疗纤维化的治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
背景情况:
- 德克-1是一种模式识别受体,对免疫平衡至关重要.
- 它在慢性病 (CKD) 病原发生中的作用目前尚不清楚.
- 慢性病的特征是渐进的纤维化和功能障碍.
研究的目的:
- 调查Dectin-1在CKD纤维化发展和进展中的作用.
- 阐明Dectin-1影响损伤的潜在机制.
- 在CKD的临床前模型中评估Dectin-1抑制的治疗潜力.
主要方法:
- 从CKD患者的脏活检中对Dectin-1表达的分析.
- 使用基因Dectin-1删除模型 (全球和巨细胞特异性) 在遭受单边尿管阻塞 (UUO) 和缺血-再输液 (IR) 损伤的小鼠中.
- 研究包括Syk/NF-κB/CCL2-CCR2和TGF-β/Smad在内的信号通路.
- 在UUO和IR小鼠模型中使用Laminarin,一种Dectin-1的药理抑制剂.
主要成果:
- 在CKD患者的纤维化脏中,dectin-1的表达显著上调,与纤维化严重程度和功能障碍相关.
- 在UUO和IR模型中,Dectin-1减弱纤维化的遗传删除.
- 宏细胞特异性去除Dectin-1证实了其在促进纤维化中的细胞自主作用.
- 发现Dectin-1通过Syk/NF-κB/CCL2-CCR2通路增强了巨细胞的透,并通过TGF-β/Smad信号传递促进了巨细胞到肌纤维细胞的过渡 (MMT).
- 在临床前模型中,用拉米纳林抑制Dectin-1的药理抑制减少了纤维化.
结论:
- 德克-1在促进慢性病中的纤维化和巨驱动炎症方面发挥着至关重要的作用.
- 向Dectin-1,特别是在巨细胞中,代表了一种有前途的治疗策略,用于减轻慢性病中的纤维化和功能障碍.
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