通过YAP/TAZ-TEADs,FAK调解机械信号,以维持上皮质平衡
Yang Peng1, Qiuyun Yuan1, Shuting Zhou1
1State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus and Research Unit of Oral Carcinogenesis and Management and Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
焦点粘附激酶 (FAK) 是通过调节YAP/TAZ活性来维持上皮平衡的关键. 抑制FAK会破坏这个过程,导致细胞分化增加,影响上皮干细胞功能.
科学领域:
- 细胞生物学 细胞生物学
- 组织工程是组织工程.
- 机械生物学 机械生物学
背景情况:
- 表皮平衡对于组织功能至关重要,并依赖于机械信号.
- 酵母和同类TAZ (YAP/TAZ) 是表皮平衡的关键机械传感器.
- 上游调节器将机械信号传递给YAP/TAZ,目前尚不清楚.
研究的目的:
- 为了确定关键的调节器介导机械信号到YAP/TAZ,以表皮平衡.
- 阐明焦粘附激酶 (FAK) 在这个信号通路中的作用.
主要方法:
- 免疫组织化学与YAP/TAZ激活相关联机械信号.
- 在HaCaT细胞和小鼠初级上皮细胞中抑制FAK.
- 抑制了YAP/TAZ-TEADs相互作用的发生.
- 在实验室中重建初级小鼠上皮细胞.
主要成果:
- 与YAP/TAZ激活和基底状态维护相关的机械信号.
- 在HaCaT细胞中,FAK抑制抑制了YAP/TAZ激活.
- 抑制YAP/TAZ-TEADs的相互作用诱导了HaCaT细胞分化.
- 重建表皮中的FAK抑制降低了YAP/TAZ活性,并增加了基底层细胞分化.
结论:
- 法克为雅普/塔兹提供机械信号.
- FAK对于通过YAP/TAZ-TEADs通路维持上皮质平衡至关重要.
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