CTNNAL1通过RhoA/ROCK1通路促进支气管上皮细胞的结构完整性
Caixia Liu1,2, Jinmei Wang2, Yurong Tan2
1Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China.
Acta biochimica et biophysica Sinica
|April 11, 2024
概括
素α类1 (CTNNAL1) 对于呼吸道上皮质完整性至关重要. 它的缺失导致结构损伤和细胞粘附减弱,可能通过RhoA/ROCK1通路,影响呼吸系统健康.
科学领域:
- 肺部生物学 肺部生物学
- 细胞粘附机制 细胞粘附机制
- 皮质生物学 皮质生物学
背景情况:
- 粘附分子对于气道上皮质在压力下的结构完整性至关重要.
- 素α类1 (CTNNAL1) 之前在喘模型中被发现是下调的,在臭氧压力的人类支气管上皮细胞 (HBEC) 中是上调的.
研究的目的:
- 研究CTNNAL1在HBECs结构粘附中的作用.
- 阐明CTNNAL1在呼吸道上皮质中的作用的基础分子机制.
主要方法:
- 使用CTNAL1-RNAi重组腺相关病毒 (AAV) 构建CTNNAL1淘汰赛 (CTNNAL1‒/‒) 鼠标模型.
- 使用CTNNAL1-siRNA开发一种CTNNAL1-抑制HBEC细胞系.
- 血素和欧 (HE) 染色用于结构分析.
- 评估细胞增殖,细胞外基质和细胞间粘附.
- 对粘附分子表达的分析 (E-cadherin,整合素β1,整合素β4) 和RhoA/ROCK1通路组件.
- 使用Y27632.2.使用ROCK的药理抑制.
主要成果:
- CTNNAL1 ‒/‒小鼠表现出脱落的上皮细胞和呼吸道结构损伤.
- 在HBEC中,CTNNAL1沉默降低了细胞增殖和细胞-细胞和细胞矩阵粘附的受损.
- 在CTNNAL1沉默的臭氧处理细胞中,E-cadherin,整合素β1和整合素β4的表达显著下降.
- 在CTNNAL1沉默后,RhoA/ROCK1通路活性下降.
- 在CTNNAL1-过度表达HBECs中,ROCK抑制 (Y27632) 逆转了臭氧诱导的粘附分子下调.
结论:
- CTNNAL1对于维持气道上皮质结构完整性至关重要,特别是在臭氧暴露下.
- CTNNAL1影响表皮细胞骨动力学,并通过RhoA/ROCK1通路调节粘附分子.
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