中脑星细胞衍生的神经营养因子的缺乏在小鼠中加剧了急性胰腺炎
bioRxiv : the preprint server for biology
|August 6, 2025
概括
中脑星细胞衍生神经营养因子 (MANF) 缺乏会使急性胰腺炎 (AP) 损伤恶化. 在胰腺应激反应和炎症中,MANF起着关键的,性别特异性的作用,可能作为AP的遗传因素.
科学领域:
- 胃肠病学和肝病学
- 分子和细胞生物学分子和细胞生物学
- 遗传学和基因组学 遗传学和基因组学
背景情况:
- 急性胰腺炎 (AP) 是一种严重的炎症疾病,具有已知的环境风险因素,但遗传易感性也与之有关.
- 细胞内膜网膜 (ER) 压力是AP病变发生的关键机制,影响蛋白质平衡 (蛋白质平衡).
- 介脑星细胞衍生神经变因子 (MANF) 是一种ER压力诱导蛋白质,对蛋白质稳定至关重要,但其在AP中的作用尚不清楚.
研究的目的:
- 调查MANF在急性胰腺炎的发病过程中的功能性作用.
- 为了确定MANF缺乏是否影响AP严重程度和相关的细胞应激反应.
- 在AP模型中探索MANF对性别特异性的潜在影响.
主要方法:
- 使用Cre/loxP系统生成胰腺特异性MANF淘汰 (MANF-KO) 的小鼠.
- 在MANF-KO和对照小鼠中使用caerulein或酒精诱导实验AP.
- 评估了胰腺损伤,亡,ER压力标志物,炎症,再生和氧化应激.
主要成果:
- 在两种AP模型中,MANF缺乏会加剧胰腺损伤,亡,ER压力,炎症和脂酶水平.
- 与雌性相比,雄性MANF-KO小鼠表现出增强的炎症,巨细胞透和氧化应激.
- 酒精诱导的AP显示了ER压力,亡,炎症和脂酶在两性中都增加,男性特异性增加了HMGB1和氧化压力.
结论:
- 在急性胰腺炎期间,MANF在减轻胰腺损伤和压力反应方面发挥着关键作用.
- 在AP中MANF的保护功能是性别特异的,男性在MANF缺乏时表现出高度的炎症和氧化应激反应.
- 这些发现突出了MANF作为潜在的内在遗传因素,有助于AP的发病和严重程度.
相关概念视频
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Pancreatitis is inflammation of the pancreas, an organ located behind the stomach. It can be either acute or chronic.
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