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局部生长激素促进结肠衰老的表皮微环境

Vera Chesnokova¹, Svetlana Zonis¹, Richard Ainsworth²

¹Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, Cedars-Sinai Medical Center, Los Angeles, California, USA.

|August 5, 2025

概括

局部生长激素 (GH) 通过促进表皮细胞-介质细胞过渡和改变细胞外基质来加速结肠衰老. 这一由衰老细胞驱动的过程会影响DNA修复,在衰老的结肠微环境中可能增加细胞转化风险.

科学领域:

胃肠病学胃肠病学
细胞生物学细胞生物学
衰老研究研究衰老研究

背景情况:

衰老与衰老细胞及其分泌的因素有关,创造了一个促进衰老的微环境.
衰老的结肠上皮细胞产生局部非垂体生长激素 (npGH).
在结肠的非瘤微环境中,npGH作用的机制需要阐明.

研究的目的:

调查局部非垂体生长激素 (npGH) 在衰老的结肠微环境中的作用机制.
确定npGH如何影响结肠细胞行为和组织结构.

主要方法:

利用人类结肠细胞 (hNCC) 和3D肠道器官,其中一些被设计成表达人类生长激素 (hGH).
在暴露于偏性npGH的有机体上进行了基因本体学和通路分析.
分析了蛋白变化,上皮细胞-介质细胞过渡标记 (E-cadherin,Twist2),细胞迁移和整个外体序列.

主要成果:

偏性npGH扭曲了细胞外基质 (ECM) 和焦点粘附通路,改变了ECM和细胞骨蛋白质.
暴露于npGH诱导了细胞骨和细胞迁移途径中的显著蛋白变化.
npGH激活了表皮-介质细胞过渡,抑制了E-cadherin,诱导了Twist2,并增加了结肠细胞迁移.
npGH抑制了DNA损伤的修复,导致结构变异增加,有利于细胞转化.

结论:

当地生长激素 (GH) 驱动结肠上皮微环境的衰老.
npGH促进结肠细胞迁移和上皮-介质细胞过渡.
通过GH抑制DNA修复可能有助于与年龄相关的结肠细胞转化.

关键词:

老化的老化衰老的老化表皮细胞-介质细胞过渡.细胞外矩阵是细胞外矩阵.增长激素增长激素的使用方法

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