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Updated: Jun 26, 2025

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非垂体生长激素使结肠细胞能够逃避衰老
Vera Chesnokova1, Svetlana Zonis1, Tugce Apaydin1
1Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Aging cell
|May 9, 2024
概括
在衰老的结肠细胞中,局部生长激素 (GH) 抑制p53,促进细胞循环的重新进入和转化. 这种GH作用,一种与衰老相关的分泌表型 (SASP) 组成部分,驱动与年龄相关的上皮细胞变化.
科学领域:
- 细胞衰老 细胞衰老
- 癌症生物学 癌症生物学
- 内分泌学 在内分泌学.
背景情况:
- DNA 损伤触发细胞衰老,最初由p53.3调节.
- 衰老细胞释放SASP,影响微环境并可能促进癌症.
- 当地激素在衰老和转变中的作用仍然不完全理解.
研究的目的:
- 调查局部非垂体生长激素 (npGH) 作为SASP成分的作用.
- 确定npGH如何影响p53活动,衰老逃避和细胞转化.
- 阐明将GH,SASP和上皮细胞转化联系在一起的机制.
主要方法:
- 使用的正常人结肠细胞 (hNCC) 和肠道器官.
- 诱导衰老和分析npGH表达及其对p53的影响.
- 评估了细胞循环重新进入标记物 (Ki67,BrdU),上皮细胞转变为介质细胞转变 (EMT) 和运动性.
- 使用异种移植和GH受体淘汰的小鼠模型.
主要成果:
- 衰老的hNCC诱导了局部npGH,这是一个抑制p53.3的SASP因子.
- 通过npGH介导的p53抑制导致衰老逃避,细胞循环重新进入和EMT.
- 获得GH分泌异源移植和衰老后细胞的小鼠表现出转移的增加.
- 通过CXCL1识别了npGH诱导和随后的CXCL1/-NFκB的GH抑制.
结论:
- 局部npGH是一种新的SASP成分,促进衰老逃避和上皮细胞转化.
- GH信号传递在调节DNA受损细胞的微环境方面发挥着至关重要的作用.
- 这项研究揭示了一个不被欣赏的GH作用,有利于与年龄相关的上皮细胞转化.
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