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肌肉细胞衍生的Ccl8是骨肌肉再生的负调节者

A Boss-Kennedy¹, D Kim¹, P Barai¹

¹Department of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

|July 25, 2024

概括

肌肉细胞衍生的Chemokine C-C动机连接体8 (Ccl8) 抑制肌肉再生. 在肌源性原生细胞中减少Ccl8会加速受伤后的肌肉修复,揭示了它在调节肌肉分化中的作用.

科学领域:

肌肉的再生和修复.
细胞和分子生物学是细胞和分子生物学.
免疫学免疫学免疫学

背景情况:

骨肌肉再生对于受伤后的恢复至关重要.
免疫细胞和细胞因子调节肌肉的修复.
化学基因C-C动机配体8 (Ccl8) 涉及到可以抑制肌肉再生的炎症反应.

研究的目的:

研究肌肉细胞衍生Ccl8在肌肉发育和肌肉再生中的作用.
确定肌肉细胞分泌的Ccl8是否影响肌肉干细胞的分化.

主要方法:

在C2C12神经细胞中对Ccl8进行 Knockdown,以评估分化.
对单细胞转录基因数据集的分析,以确定免疫细胞和肌肉干细胞 (MuSCs) 中的Ccl8表达.
在生体中,CRISPR-Cas9基因编辑在小鼠的Pax7+,Myf5+和MyoD+肌源性原生细胞 (MPC) 中,以耗尽Ccl8.8.
在小鼠的化诱导的肌肉损伤模型.
用重组Ccl8来评估其对再生的影响.

主要成果:

降低了Ccl8,但没有Ccl2或Ccl7,增加了C2C12髓细胞分化.
在再生肌肉中,Ccl8由免疫细胞和MuSC表达,具有明显的时间模式.
在Pax7+,Myf5+或MyoD+MPC中Ccl8的耗尽加速了年轻和中年老鼠的肌肉再生.
再组合Ccl8的使用逆转了加速再生的表型.

结论:

肌肉细胞衍生出的Ccl8在调节肌原分化的启动方面发挥着重要作用.
Ccl8作为损伤诱导的肌肉再生的负调节剂.
准肌肉细胞衍生的Ccl8可能为增强肌肉修复提供治疗策略.

关键词:

在Ccl8中使用.肌源性原始细胞的前代细胞这就是我的okine.卫星细胞卫星细胞卫星细胞.骨肌肉的再生和再生

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