分泌的GDF15在人类β细胞的DNA损伤中介衰老过程中维持转录反应
Nayara Rampazzo Morelli1,2, Camille Préfontaine1,2, Jasmine Pipella1,2
1Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme, Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada.
American journal of physiology. Endocrinology and metabolism
|August 28, 2024
概括
增长分化因子15 (GDF15) 在1型糖尿病中对衰老β细胞存活不至关重要. 然而,GDF15对于维持人类β细胞中与细胞衰老相关的基因表达模式至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
背景情况:
- 1型糖尿病 (T1D) 涉及胰腺β细胞的自身免疫破坏.
- 贝塔细胞的应激反应,包括衰老和与衰老相关的分泌表型 (SASP),有助于T1D的发病.
- 增长分化因子15 (GDF15) 是一种关键的SASP因子,在衰老的β细胞中被发现.
研究的目的:
- 调查分泌的GDF15在衰老的人类β细胞在T1D相关的DNA损伤条件下的生存和转录调节中的作用.
- 确定GDF15是否对于维持衰老的人类小岛和β细胞的生存能力至关重要.
主要方法:
- 利用DNA损伤模型在人类小岛和EndoC-βH5β细胞中诱导衰老.
- 测量了来自T1D捐赠者的衰老β细胞中的GDF15分泌.
- 采用基于抗体的中和来阻止GDF15的活动.
- 评估细胞活力和分析衰老相关基因的表达.
主要成果:
- 从T1D捐赠者的衰老β细胞中观察到高GDF15分泌.
- 中和GDF15并没有影响衰老的人类小岛或β细胞的活力.
- GDF15中和导致衰老相关基因的表达减少,包括GDF15和BCL2L1.
结论:
- 分泌的GDF15不需要老化的人类β细胞的生存.
- GDF15在维持与人类β细胞衰老相关的转录反应方面发挥着至关重要的作用.
- 这些发现突出了GDF15在调节衰老程序中的功能,而不是T1Dβ细胞中的细胞存活.
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