RhoA/ROCK 通路和 MYOCD 在哮喘气道重塑中的功能

IF 2.5 4区 医学 Q3 ALLERGY International Archives of Allergy and Immunology Pub Date : 2024-09-11 DOI:10.1159/000540963
Yunfei Cui,Chendi Yu,Qinghua Lu,Xiao Huang,Weinan Lin,Ting Huang,Lichao Cao,Qin Yang
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引用次数: 0

摘要

简介:哮喘是一种常见的慢性呼吸系统疾病,以慢性气道炎症和气道异常重塑为特征。RhoA/ROCK 通路和肌钙蛋白相关转录因子 A(MRTF-A)与气道平滑肌细胞(ASCMs)的增殖密切相关,而气道平滑肌细胞的增殖与气道重塑过程密切相关。MYOCD与MRTF-A同源,但在平滑肌细胞中特异性表达,可能调节RhoA/ROCK激活的细胞增殖和随后的气道重塑。结果对照组过表达/沉默细胞系与ROCK过表达/沉默细胞系比较发现,MYOCD与细胞骨架和RhoA/ROCK通路呈现一致的变化趋势。ROCK1 可促进 ASCMs 的增殖和迁移。结论我们的研究表明,Rho/ROCK/MYOCD 是参与气道平滑肌细胞迁移和增殖的关键通路。我们的研究表明,Rho/ROCK/MYOCD 是参与气道平滑肌细胞迁移和增殖的关键通路。抑制 Rho/ROCK 可能是打破哮喘 ASCMs 增殖恶性循环的有效方法,为治疗哮喘气道重塑提供了一种新策略。
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The Function of RhoA/ROCK Pathway and MYOCD in Airway Remodeling in Asthma.
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.
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
105
审稿时长
2 months
期刊介绍: ''International Archives of Allergy and Immunology'' provides a forum for basic and clinical research in modern molecular and cellular allergology and immunology. Appearing monthly, the journal publishes original work in the fields of allergy, immunopathology, immunogenetics, immunopharmacology, immunoendocrinology, tumor immunology, mucosal immunity, transplantation and immunology of infectious and connective tissue diseases.
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