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Published on: October 13, 2019
CTNNAL1 promotes the structural integrity of bronchial epithelial cells through the RhoA/ROCK1 pathway
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.
Catenin alpha-like 1 (CTNNAL1) is crucial for airway epithelial integrity. Its absence causes structural damage and weakened cell adhesion, potentially via the RhoA/ROCK1 pathway, impacting respiratory health.
Area of Science:
- Pulmonary biology
- Cellular adhesion mechanisms
- Epithelial biology
Background:
- Adhesion molecules are vital for airway epithelial structural integrity under stress.
- Catenin alpha-like 1 (CTNNAL1) was previously found downregulated in asthma models and upregulated in ozone-stressed human bronchial epithelial cells (HBECs).
Purpose of the Study:
- To investigate the role of CTNNAL1 in the structural adhesion of HBECs.
- To elucidate the underlying molecular mechanisms of CTNNAL1's function in airway epithelium.
Main Methods:
- Construction of a CTNNAL1 knockout (CTNNAL1 ‒/‒) mouse model using CTNNAL1-RNAi recombinant adeno-associated virus (AAV).
- Development of a CTNNAL1-silencing HBEC cell line using CTNNAL1-siRNA.
- Hematoxylin and eosin (HE) staining for structural analysis.
- Assessment of cell proliferation, extracellular matrix, and intercellular adhesion.
- Analysis of adhesion molecule expression (E-cadherin, integrin β1, integrin β4) and RhoA/ROCK1 pathway components.
- Pharmacological inhibition of ROCK using Y27632.
Main Results:
- CTNNAL1 ‒/‒ mice exhibited denuded epithelial cells and airway structural damage.
- CTNNAL1 silencing in HBECs reduced cell proliferation and impaired cell-cell and cell-matrix adhesion.
- Expressions of E-cadherin, integrin β1, and integrin β4 were significantly decreased in ozone-treated cells with CTNNAL1 silencing.
- RhoA/ROCK1 pathway activity decreased upon CTNNAL1 silencing.
- ROCK inhibition (Y27632) reversed ozone-induced adhesion molecule downregulation in CTNNAL1-overexpressing HBECs.
Conclusions:
- CTNNAL1 is essential for maintaining airway epithelial structural integrity, particularly under ozone exposure.
- CTNNAL1 influences epithelial cytoskeleton dynamics and regulates adhesion molecules through the RhoA/ROCK1 pathway.
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