希波终端效应器YAP在1型糖尿病中增强了肠道病毒的复制
Shirin Geravandi1, Huan Liu1, Heena Pahwa1
1University of Bremen, Islet Biology Laboratory, Centre for Biomolecular Interactions Bremen, Bremen, Germany.
Nature communications
|October 6, 2025
概括
是的相关蛋白 (YAP) 在1型糖尿病 (T1D) 胰腺上调,并促进coxsackievirus B (CVB) 复制. 抑制YAP可能为T1D提供一种新的抗病毒策略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 肠道病毒感染,特别是Coxsackievirus B (CVB),与1型糖尿病 (T1D) 的风险有关.
- 驱动病毒诱导的小岛自身免疫的特定细胞宿主因素尚未完全理解.
研究的目的:
- 调查Hippo通路效应者的Yes相关蛋白 (YAP) 在肠道病毒诱导的胰腺小岛自身免疫中的作用.
- 探索YAP作为T1D的潜在治疗点.
主要方法:
- 从T1D和自身抗体阳性捐赠者的胰腺组织中分析YAP和CTGF表达.
- 评估YAP调制对CVB复制和胰腺细胞功能 in vitro和 in vivo的影响.
- 研究YAP,TEAD,MST1和CVB感染之间的机制相互作用.
主要成果:
- YAP及其点CTGF在T1D和风险人群的胰腺上调,与CVBRNA存在相关.
- 过度表达YAP增强了CVB复制,小岛炎症和β细胞亡;抑制YAP阻止了病毒复制.
- YAP通过涉及MST1.1的负反循环促进CVB放大和β细胞功能障碍.
结论:
- YAP是一种关键的宿主因子,可以放大胰腺内肠病毒感染的程度.
- 在促进病毒复制和β细胞损伤方面YAP的作用表明它是T1D预防和治疗的潜在抗病毒标.
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