类似胰岛素的生长因子1通过ERK1/2激活,通过衰老保护胃节拍细胞和运动功能
Vy Truong Thuy Nguyen1, Negar Taheri1, Egan L Choi1
1Enteric Neuroscience Program, Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Gastroenterology Research Unit, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Cellular and molecular gastroenterology and hepatology
|June 10, 2023
概括
胰岛素样生长因子1 (IGF1) 可以通过激活ERK1/2信号来预防与年龄相关的胃起器细胞 (ICC/ICC-SC) 损失. 这改善了老年小鼠的胃功能和食物摄入.
科学领域:
- 胃肠病学 胃肠病学
- 衰老研究研究 衰老研究
- 细胞生物学 细胞生物学
背景情况:
- 衰老会损害胃运动功能,减少食物摄入量,导致虚弱和肉症.
- 与年龄相关的胃功能障碍与Cajal (ICC) 的间歇细胞和神经调节细胞的丧失有关.
- 与转化相关的蛋白53抑制了ICC干细胞 (ICC-SC) 中的ERK1/2信号,导致细胞循环停止和ICC耗尽.
研究的目的:
- 调查胰岛素样生长因子1 (IGF1) 是否可以减轻老年小鼠的ICC-SC/ICC损失和胃功能障碍.
- 为了确定IGF1是否可以抵消与年龄相关的ERK1/2信号抑制在ICC-SC.
- 在加速衰老模型中评估IGF1对胃顺应,食物摄入量和体重增加的影响.
主要方法:
- 克洛托小鼠,一个加速衰老的模型,被用稳定的IGF1模拟物 (LONG R3 rhIGF1) 治疗.
- 卡哈尔 (ICC) 和ICC干细胞 (ICC-SC) 的胃间歇细胞使用流动细胞计,西斑和免疫组织化学进行了分析.
- 胃合规性被测量出活体,并评估了在ICC-SC培养物中使用nutlin 3a (诱导转化相关蛋白53) 和rhIGF1.1治疗的ERK1/2信号.
主要成果:
- 长期R3 rhIGF1治疗防止了与年龄相关的ERK1/2酸化和ICC/ICC-SC种群的衰退.
- 在克洛托小鼠中,IGF1的使用减轻了食物摄入量减少和体重增加受损.
- 在体外,rhIGF1逆转了努特林3a诱导的ERK1/2酸化减少和ICC-SC中的细胞生长停止.
结论:
- IGF1通过激活ERK1/2信号来减轻与年龄相关的ICC/ICC-SC损失.
- 在老年小鼠中,IGF1治疗改善了胃部的适应性,并增加了食物摄入量.
- 向IGF1信号可能为与年龄相关的胃功能障碍提供治疗策略.
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