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MAP3K1和EGFR信号交叉介导基因环境相互作用,阻止发育性组织关闭

Jingjing Wang¹, Bo Xiao¹, Eiki Kimura¹

¹Department of Environmental and Public Health Sciences, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA.

The Journal of biological chemistry

|June 19, 2024

概括

环境中有毒的二氧化会通过破坏关键信号通路,在患有Map3k1基因突变的小鼠中引起出生缺陷. 这些通路中的基因变异可能会增加化学物质暴露的风险.

科学领域:

发育生物学是发展生物学.
毒理学毒理学毒理学
分子生物学分子生物学

背景情况:

异常的信号传导途径会破坏组织发育,包括胚胎眼关闭.
线素激活蛋白激酶激酶激酶1 (MAP3K1) 对于眼发育至关重要;Map3k1淘汰的小鼠表现出眼缺陷.
在子宫内暴露于二氧化会在Map3k1异合的小鼠中引起类似的眼睛缺陷.

研究的目的:

为了研究Map3k1和二氧化暴露之间的基因环境 (GxE) 相互作用机制.
为了阐明参与二氧化物诱导的胚胎眼缺陷的分子途径.

主要方法:

使用了MAP3k1异合的小鼠和子宫内二氧化物暴露模型.
研究的信号通路包括阿里碳化合物受体 (Ahr),表皮生长因子受体 (Egfr) 和Jun N-终端激酶 (JNK).
在小鼠模型中使用了Ahr,Egfr,Jnk1和S1pr的基因淘汰策略.

主要成果:

通过Ahr,二氧化物激活了Egfr信号,抑制了MAP3K1依赖的JNK活动.
Map3k1异性加剧了二氧化物诱导的JNK抑制,导致眼缺陷.
Ahr或Egfr的基因淘汰改善了二氧化的毒性,而Jnk1/S1pr的淘汰则加强了它.

结论:

Ahr,Egfr和S1P-MAP3K1-JNK通路之间的交叉声调决定了二氧化碳暴露的结果.
这些关键路径中的基因突变是环境化学毒性的潜在风险因素.
研究结果突出了基因倾向与发展性毒性环境因素之间的相互作用.

关键词:

美国人权委员会 (AHR)欧洲农业基金会 (EGFR) 是一个.发育性组织关闭.二氧化二氧化的使用情况皮质形态发生的表皮形态发生.基因与环境的相互作用在S1PR-MAP3K1-JNK路径中.

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