皮肤生长因子受体激活刺激受损管外皮细胞中的SOX9表达
Jianchun Chen1,2,3, Fenfen Peng2,3, Mengdi Jiang2,3
1Department of Veterans Affairs, Nashville, Tennessee.
Journal of the American Society of Nephrology : JASN
|September 2, 2025
概括
在急性损伤 (AKI) 后,表皮生长因子受体 (EGFR) 的激活对于近管细胞的SOX9诱导至关重要. 这种机制是了解修复和慢性病 (CKD) 发展的关键.
科学领域:
- 肝脏病学
- 分子生物学
- 细胞生物学
背景情况:
- 在急性损伤 (AKI) 后,SOX9表达在近管细胞 (RPTC) 中至关重要.
- 在RPTC中持续的SOX9上调与慢性病 (CKD) 的发展有关.
- 通过损伤诱导SOX9的机制需要进一步阐明.
研究的目的:
- 研究表皮生长因子受体 (EGFR) 在受损RPTC中调节SOX9表达的作用.
- 在损伤的背景下,阐明将EGFR激活与SOX9诱导联系在一起的分子途径.
主要方法:
- 检查了急性管道损伤和慢性异质移植脏病患者的人类管上皮细胞中的SOX9和EGFR表达.
- 使用小鼠模型,包括缺少EGFR激酶的小鼠,研究EGFR在SOX9上调中的作用.
- 在培养的人类RPTC中研究了该机制,以确认EGFR对SOX9的影响.
主要成果:
- 在人类管上皮细胞中观察到SOX9和EGFR表达的升高和局部化.
- 在RPTC中hHB-EGF的过度表达增加了SOX9,在EGFR缺乏的小鼠中这种效应被消除了.
- 在缺血性AKI之后,EGFR抑制 (遗传或药理) 降低了SOX9表达.
- 缺血性AKI激活了邻近管 EGFR,启动了Akt- YAP/ TAZ- TEAD通路和SOX9诱导.
结论:
- 在AKI之后,EGFR激活是RPTC中SOX9表达的关键调节者.
- 在损伤反应中,EGFR-Akt-YAP/TAZ-TEAD信号轴介导SOX9诱导.
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