在非帕伦基马肝细胞区的动态YAP表达控制异质细胞通信
Kaijing Liu1,2,3, Lilija Wehling2,4, Shan Wan5
1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangdong, China.
Cellular and molecular life sciences : CMLS
|March 4, 2024
概括
肝细胞中的YAP无活化会导致损伤,而TAZ缺失会减少这种效应. 在非帕伦基马细胞中YAP激活会影响细胞通信和炎症.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 包括YAP和具有PDZ结合动机 (TAZ) 的转录协活性剂在内的Hippo通路是癌症治疗中的关键调节器.
- 了解YAP和TAZ之间的补偿机制至关重要.
- YAP/TAZ干扰对非恶性肝细胞通信的影响尚不清楚.
研究的目的:
- 为了研究由YAP和TAZ无活化引起的肝脏特异性表型.
- 为了确定TAZ删除是否影响YAP诱导的肝损伤.
- 探索YAP/TAZ在非共生细胞通信中的作用.
主要方法:
- 产生具有肝细胞 (HC) 和胆道上皮细胞 (BEC) 特定YAP和TAZ删除 (YAPKO,TAZKO,DKO) 的小鼠.
- 使用免疫组织化学,单细胞测序和蛋白质组学分析肝脏组织和血清.
- 评估YAP表达在非辅酶细胞 (NPCs) 的消耗后.
主要成果:
- 在HC和BEC中YAP无活化导致BEC损失,肝纤维化和亡,TAZ缺失减轻了这些影响.
- 在NPC (Kupffer细胞,内皮细胞) 中诱导YAP表达独立于胆固醇酶.
- 在YAPKO小鼠中观察到血清中增高的促炎因素 (CXCL11,FLT3L,ICAM1).
结论:
- 肝细胞中的YAP无活化会导致损伤,而TAZ缺失不会增强,而是减少这种表型.
- 在NPC中YAP激活代表了一种新的机制,有助于肝炎.
- 这项研究强调了YAP在NPC介导的细胞通信中的作用.
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