ECM和细胞-细胞粘附之间的协调调节了岛屿聚合,架构和功能成熟的发展
Wilma Tixi1, Maricela Maldonado1,2, Ya-Ting Chang1
1Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United States.
eLife
|August 23, 2023
概括
发育中的胰岛通过细胞外基质信号传递和细胞-细胞粘附来聚合. 破坏这些相互作用会损害岛屿形成和内分泌细胞成熟,揭示关键的自我组织机制.
科学领域:
- 内分泌学和发育生物学
- 细胞生物学和组织架构.
背景情况:
- 胰腺小岛是重要的内分泌细胞聚合物,对代谢调节至关重要.
- 发展中的小岛屿的自我组织和聚合的机制仍然不太清楚.
- 了解小岛聚合是解决糖尿病等代谢疾病的关键.
研究的目的:
- 在发育过程中阐明调节胰腺小岛聚合的分子机制.
- 研究细胞外矩阵 (ECM) 信号传递和细胞-细胞粘附在岛屿形成中的作用.
- 确定这些因素对小岛架构和内分泌功能的影响.
主要方法:
- 利用基因动物模型与向基因失活.
- 采用先进的成像技术来可视化小岛屿的发展.
- 进行基因表达分析,以分析分子变化.
- 研究了整合素β1 (ECM受体) 和α-catenin (细胞粘附分子) 的功能.
主要成果:
- 在内分泌细胞中禁用整合素β1破坏了血管相互作用,但增强了细胞-细胞粘附和岛屿大小.
- 切除α-catenin促进了血管相互作用,但损害了小岛集群.
- 同时不激活整合素β1和α-catenin严重破坏了岛屿聚合和内分泌细胞成熟.
结论:
- 岛屿聚合是一个严格规范的过程,涉及ECM信号和细胞-细胞粘附之间的平衡.
- 集成蛋白β1和α-catenin在建立小岛架构方面发挥了对立而又合作的作用.
- 适当的小岛聚合对于小岛内的内分泌细胞的功能成熟至关重要.
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