BAF60C通过控制Reg3b mRNA衰变,将核应激与2型糖尿病中的β细胞功能障碍联系起来
Zhuoying Yang1, Shuaishuai Zhu1, Cheng-An Lyu2
1Department of Pathology and Pathophysiology and Department of General Surgery, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, Zhejiang 313000, China; Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Developmental cell
|March 10, 2026
概括
这项研究表明,胰腺β细胞中BAF60C的减少会通过增加炎症和核应激,使2型糖尿病 (T2D) 恶化. 恢复BAF60C-REG3B通路可以改善糖尿病小鼠的葡萄糖控制.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 岛屿免疫微环境在2型糖尿病 (T2D) 病原发生过程中至关重要.
- 将β细胞功能障碍与小岛炎症联系起来的调控机制尚未完全理解.
研究的目的:
- 为了研究BAF60C的作用,一个染色体重塑剂,在β细胞功能障碍和T2D.
- 阐明BAF60C影响岛屿炎症和葡萄糖平衡的机制.
主要方法:
- 在T2D患者和糖尿病小鼠中分析BAF60C表达.
- 产生β细胞特异性BAF60C淘汰和过度表达的小鼠模型.
- 评估高血糖症,核细胞应激和小岛炎症.
- 研究BAF60C与NPM1和Reg3bmRNA的相互作用.
- 在糖尿病小鼠中对REG3B补充剂和运动干预措施的评估.
主要成果:
- 降低BAF60C表达与β细胞功能障碍,核应激和T2D炎症相关.
- BAF60C缺乏会加剧饮食引起的糖尿病,而其过度表达则具有保护作用.
- BAF60C通过促进REG3B的表达和分泌来抑制炎症,调节β细胞和巨细胞的交叉交流.
- BAF60C与NPM1和Reg3bmRNA相互作用,以调节Reg3bmRNA的衰变.
- 补充REG3B或炼可以改善葡萄糖平衡,并减少肥胖和T2D小鼠的炎症.
结论:
- BAF60C通过REG3B通路抑制小岛炎症,在T2D中起着保护作用.
- BAF60C通过涉及RNA处理的非正规机制将核应激与β细胞衰竭联系起来.
- 针对BAF60C-REG3B轴为T2D提供了一个潜在的治疗策略.
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