p120-catenin调解了皮肤中的炎症反应
Mirna Perez-Moreno1, Michael A Davis, Ellen Wong
1Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
在小鼠皮肤中的p120-catenin损失导致炎症和表皮增生,不是通过影响附着结,而是通过核因子kappa B (NFkB) 激活. 这项研究揭示了p120
科学领域:
- 细胞生物学 细胞生物学
- 皮肤病学 皮肤病学
- 免疫学 免疫学 免疫学
背景情况:
- 已知p120-catenin可以稳定细胞培养中的附着结 (AJ).
- 在较低的真核生物体内的体内研究没有确定p120-catenin的作用.
- 哺乳动物表皮中的p120-catenin体内功能尚不清楚.
研究的目的:
- 为了研究p120-catenin在小鼠表皮的体内功能.
- 为了确定p120-catenin缺乏在皮肤平衡中的后果.
- 阐明p120-catenin在表皮调节中的作用背后的分子机制.
主要方法:
- 条件基因向在小鼠中,以创建p120虚表皮.
- 对表皮结构,屏障功能和细胞间粘附的分析.
- 皮肤移植实验和用抗炎药物治疗.
- 核因子卡帕B (NFkB) 激活的体外和体内评估.
- 通过p120-catenin.catenin对Rho GTPase调节的研究.
主要成果:
- 新生儿p120无皮表皮表现出减少的AJ成分,但完整的屏障功能.
- 衰老的p120 null小鼠出现了表皮增生,慢性炎症,头发退化和脂肪流失.
- 这些表型与NFkB激活有关,而不是减少结点蛋白.
- p120 无表皮细胞表现出核NFkB激活和下游炎症点.
- p120-catenin 影响NFkB的激活和免疫恒常,部分是通过Rho GTPases.
结论:
- 在维护皮肤免疫恒常状态方面,p120-catenin在体内发挥着至关重要的作用.
- 皮肤上p120-catenin缺乏导致NFkB驱动的炎症和增生.
- 调节Rho GTPases是p120-catenin影响皮肤免疫反应的关键机制.
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