Abstract
Introduction: Asthma is a common chronic respiratory disease characterized by chronic airway inflammation and abnormal airway remodeling. The RhoA/ROCK pathway and myocardin-related transcription factor A (MRTF-A) demonstrate significant associations with the proliferation of airway smooth muscle cells (ASCMs), which tightly correlates with the process of airway remodeling. MYOCD, which is homologous to MRTF-A but specifically expressed in smooth muscle cells, potentially regulates RhoA/ROCK activated cell proliferation and subsequent airway remodeling. Methods: The RhoA/ROCK overexpression and silencing cell lines were constructed in vitro, as well as MYOCD overexpression/silencing. The cytoskeleton alterations induced by RhoA/ROCK pathway were identified by the measuring of globular actin and filamentous actin. Results: The comparison between controls for overexpression/silencing and ROCK overexpression/silencing revealed that MYOCD presented consistent change trends with cytoskeleton and RhoA/ROCK pathway. The ROCK1 facilitates the proliferation and migration of ASCMs. The MYOCD enhanced the proliferation and migration of HASMCs. Conclusion: Our study indicates that Rho/ROCK/MYOCD is a key pathway involved in the migration and proliferation of airway smooth muscle cells. Inhibition of Rho/ROCK may be an effective approach to breaking the vicious cycle of asthmatic ASCMs proliferation, providing a novel strategy in treating asthma airway remodeling.
Plain Language Summary
Asthma is a common chronic respiratory disease characterized by chronic airway inflammation and abnormal airway remodeling. The regulation process of RhoA/ROCK signaling pathway and downstream MRTF-A gene is well studied and exhibits significant associations with cell contraction and cell proliferation, which correlates tightly with airway remodeling. While most studies focusing on the MRTF-A to clarify the mechanism of cell growth, we paid close attention to MYOCD gene, which shares homology with MRTF-A but expressed specifically in smooth muscle cells. Through the series cell experiments, molecular assays, and literature review, we firstly illustrated the potential function of MYOCD underlying the regulation of RhoA/ROCK activated cell proliferation and subsequent airway remodeling in airway smooth muscle cells. This novel sight provides therapeutic targets for asthma.
