在携带选择性遗传失效性CXCL12/蛋白质甘氨酸相互作用的小鼠中,恒常性和组织修复缺陷
Patricia Rueda1, Adèle Richart, Alice Récalde
1Institut Pasteur, Unité de Pathogénie Virale, Département de Virologie, INSERM U819, Paris, France.
Circulation
|October 5, 2012
概括
像CXCL12这样的化学激素通过肝素硫酸盐对细胞信号进行固定. 破坏这种相互作用会损害再血管化,证明其在组织修复和化基因功能中的关键作用.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 化基因与硫酸肝素蛋白质糖相互作用,在细胞表面和细胞外基质上固定.
- 这种相互作用对于细胞定位和信号传输至关重要,但其体内影响尚未完全理解.
研究的目的:
- 为了研究肝素硫酸盐相互作用在内源化基因功能中的作用,在体内.
- 了解受损的化学激素固定对生理和病理过程的影响.
主要方法:
- 设计了一种小鼠模型 (Cxcl12(Gagtm)) 具有一种突变,阻止了肝硫酸盐结合,但保留了CXCR4信号传递.
- 分析了Cxcl12(Gagtm/Gagtm) 小鼠的正常发育,造血前体细胞数量,以及对诱导的急性缺血的反应.
- 用外源CXCL12γ及其突变来评估突变小鼠的再血管化能力.
主要成果:
- Cxcl12 (((Gagtm/Gagtm) 的小鼠表现出正常发育和循环中的CD34 ((+) 细胞的增加.
- 在突变小鼠的缺血组织中观察到,尽管CXCL12表达高,但重血管化受损和细胞透减少.
- 外源性CXCL12γ恢复了血管生长,而非结合性突变体则没有这样做.
结论:
- 肝素硫酸盐相互作用对于CXCL12在恒温和疾病中的功能至关重要.
- 首次展示了化学激素固定化的体内模式.
- 突出了向化基因-海帕兰硫酸盐相互作用的治疗潜力.
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