巨细胞-肌纤维细胞过渡作为骨肌肉纤维化受伤后通过补充系统激活的潜在来源
Beijie Qi1, Yuqi Li2, Zhen Peng2
1Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.
Journal of inflammation research
|February 22, 2024
概括
大细胞-肌纤维细胞过渡 (MMT) 在受伤后发生在骨肌肉中,导致纤维化. 这一涉及补体系统的过程在受伤后五天达到顶峰,并为抗纤维菌疗法提供了目标.
科学领域:
- 骨肌肉的再生和修复.
- 细胞的可塑性和分化.
- 纤维化和组织重塑.
背景情况:
- 骨肌损伤通常会导致肌纤维细胞的纤维化,阻碍完全恢复.
- 这些肌纤维细胞的起源对于开发抗纤维细胞策略至关重要.
- 巨细胞-肌纤维细胞过渡 (MMT) 与器官纤维化有关,但其在骨肌肉中的作用尚不清楚.
研究的目的:
- 研究急性损伤后骨肌中巨细胞-肌纤维细胞过渡 (MMT) 的存在和机制.
- 鉴定导致骨肌肉纤维化的肌纤维细胞的细胞起源.
- 探索补充系统在受伤的骨肌肉内MMT中的作用.
主要方法:
- 在急性损伤后对小鼠骨肌的单细胞转录组分析.
- 细胞与细胞相互作用的分析,伪时间轨迹,基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG).
- 在体内和体外实验验证,包括组织学研究和骨髓衍生巨细胞 (BMDMs) 的C3a刺激.
主要成果:
- 单细胞转录组数据揭示了受伤后巨细胞和肌纤维细胞之间的显著相互作用.
- 大细胞-肌纤维细胞过渡 (MMT) 细胞 (CD68+α-SMA+) 在受伤后五天突出,下降了14天.
- 补充系统,高调的C3ar1,C1qa,C1qb和C1qc,与MMT有关,C3a在BMDM中直接诱导MMT.
结论:
- 巨细胞-肌纤维细胞过渡 (MMT) 在急性损伤后发生在骨肌肉中,可能导致纤维化.
- MMT是损伤后大约五天发生的重大事件,并由补充系统调节.
- 需要进一步的研究来确认MMT在骨肌肉纤维化中的直接亲纤维作用.
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