单细胞和空间转录学定义了脏损伤后的抗炎和亲纤维菌利基
Li Li1,2, Jinlin Liao1,2, Yuxi Zhang1,2
1State Key Laboratory of Multi-organ Injury Prevention and Treatment, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 3, 2025
概括
素C (TNC) 通过通过托尔类受体4 (TLR4) 信号来激活巨细胞来创建纤维化位. 抑制TLR4可降低脏炎症和纤维化,提供潜在的治疗点.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 纤维化,慢性病 (CKD) 的一个常见的结果,起源于受伤诱导的纤维化.
- 了解驱动纤维化的细胞和分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 划分细胞异质性,空间组织和纤维化脏微环境中的分子相互作用.
- 确定关键的分子参与者,指挥炎和纤维化的发展.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和空间转录组学 (ST) 用于小鼠脏,这些脏遭受了缺血-再输液损伤.
- 对TNC丰富的微环境,巨细胞激活通路 (TLR4/NF-κB) 和治疗干预 (TLR4抑制/淘汰) 的分析.
主要成果:
- 鉴定出一种富含素C (TNC) 的,促炎和益纤维素的微环境,促进巨细胞激活.
- 通过托尔类受体4 (TLR4) /NF-κB信号传递,TNC和TNC丰富的支架激活了骨髓衍生的巨细胞.
- 通过抑制巨细胞激活,对TLR4的药理抑制或遗传淘汰显著缓解了炎和纤维化.
结论:
- 素C (TNC) 在建立驱动纤维化的促炎和益纤维菌利基中发挥着关键作用.
- 通过TLR4/NF-κB信号通路激活巨细胞是TNC介导纤维化的一个关键机制.
- 向TNC-巨-TLR4轴为纤维化治疗提供了一个有前途的治疗策略.
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