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缺少Lhx6导致人类胚胎 palatal mesenchymal 细胞 mitophagy 功能障碍在口腔裂

Haotian Luo¹, Hio Cheng Ieong¹, Runze Li¹

¹Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China.

Molecular medicine (Cambridge, Mass.)

|October 22, 2024

概括

网红酸 (RA) 的过度消费会通过降低Lhx6的调节,损害线粒体功能和细胞迁移,导致口腔裂. 恢复Lhx6水平可以纠正这些缺陷,突出其在面发育中的作用.

科学领域:

发展生物学发展生物学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

过度摄入视网膜酸 (RA) 与严重的额面形有关,包括口腔裂.
RA 干扰胚胎 palatal 介质细胞 (EPM) 细胞的增殖和迁移,但机制尚不清楚.

研究的目的:

阐明RA诱导口腔裂的机制.
研究Lhx6在RA引起的面形缺陷中的作用.

主要方法:

在胎儿小鼠中建立了视网膜酸 (RA) 诱导的口腔裂纹模型.
通过各种测试 (CCK-8,EDU,伤口愈合,Transwell,Mito-Tracker,ROS,ATP,mtDNA) 评估细胞增殖,迁移和线粒体功能.
分析了基因表达 (qPCR,Western blot) 和信号通路 (生物信息学,MAPK),专注于Lhx6和线粒细胞衰变.

主要成果:

风湿性关节炎暴露损害了口腔发育,EPM细胞增殖和迁移,与线粒体功能障碍和Lhx6下调有关.
Lhx6的倒退加剧了这些缺陷,而Lhx6的过度表达改善了RA引起的功能障碍.
通过调节PINK1/Parkin介导的线粒细胞衰变和激活MAPK信号传递,Lhx6减轻了RA诱导的功能障碍.

结论:

通过PINK1/帕金介导的线粒细胞衰变和MAPK信号传递,Lhx6对于维持线粒体平衡至关重要.
由RA引起的Lhx6下调会破坏线粒体平衡,导致细胞增殖/迁移缺陷和口腔裂.

关键词:

破裂的宫殿口.胚胎的 palatal 中介细胞细胞.在Lhx6中,Lhx6是什么?线粒细胞衰变 - - 线粒细胞衰变 (mitophagy) 是一种标签:PINK1PINK1PINK1PINK1 雷蒂诺酸是什么意思雷蒂诺酸是什么意思

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