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RhoA/ROCK信号通路及MYOCD在哮喘气道重塑中的作用

The Function of RhoA/ROCK Pathway and MYOCD in Airway Remodeling in Asthma.

作者信息

Cui Yunfei, Yu Chendi, Lu Qinghua, Huang Xiao, Lin Weinan, Huang Ting, Cao Lichao, Yang Qin

机构信息

Department of Respiratory Medicine, Shenzhen Children's Hospital, Shenzhen, China.

Department of Research and Development, Shenzhen Nucleus Gene Technology Co., Ltd., Shenzhen, China,

出版信息

Int Arch Allergy Immunol. 2025;186(2):103-119. doi: 10.1159/000540963. Epub 2024 Sep 11.

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.

摘要

引言

哮喘是一种常见的慢性呼吸道疾病,其特征为慢性气道炎症和气道重塑异常。RhoA/ROCK通路和心肌相关转录因子A(MRTF-A)与气道平滑肌细胞(ASCMs)的增殖显著相关,而这与气道重塑过程紧密相关。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激活的细胞增殖及随后的气道重塑。

方法

在体外构建RhoA/ROCK过表达和沉默细胞系,以及MYOCD过表达/沉默细胞系。通过测量球状肌动蛋白和丝状肌动蛋白来鉴定由RhoA/ROCK通路诱导的细胞骨架改变。

结果

过表达/沉默对照组与ROCK过表达/沉默对照组之间的比较显示,MYOCD与细胞骨架和RhoA/ROCK通路呈现一致的变化趋势。ROCK1促进ASCMs的增殖和迁移。MYOCD增强HASMCs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。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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