mTOR介导的信号网络调控哮喘气道重塑的研究新进展

New research progress on mTOR-mediated signaling network regulating airway remodeling in asthma

关键词:  支气管哮喘(哮喘)  气道重塑  哺乳动物雷帕霉素靶蛋白  信号网络

Key words:  bronchial asthma (asthma)  airway remodeling  mammalian target of rapamycin (mTOR)  signaling networks

摘要:

哮喘是一种气道慢性炎症性疾病,慢性炎症引起的组织“损伤-修复”使气道结构发生变化,而这种病理性气道重塑是哮喘患者肺功能不可逆性降低的直接原因。哺乳动物雷帕霉素靶蛋白(mTOR)在哮喘气道杯状细胞(GC)化生与黏液高分泌、肌成纤维细胞分化与细胞外基质(ECM)形成以及平滑肌细胞(ASMCs)增生与肥大等气道重塑过程中发挥了关键的调控作用,故mTOR及其介导的信号网络调控哮喘气道重塑已成为近年来研究的新热点。本文从PIK3/AKT、AMPK及NF-κB等信号靶点的角度综述mTOR调控哮喘气道重塑的分子机制,为哮喘气道重塑机制研究以及新药研发提供理论依据。

Abstract:

Asthma is a chronic inflammatory disease of the airway, in which tissue damage repair caused by chronic inflammation leads to changes in airway structure. This pathological airway remodeling is the direct cause of irreversible decline in lung function in asthma patients. The mammalian target protein of rapamycin (mTOR) plays a key regulatory role in airway remodeling processes such as metaplasia and mucus hypersecretion in asthmatic goblet cells (GC), differentiation of myofibroblasts and formation of extracellular matrix (ECM), as well as proliferation and hypertrophy of smooth muscle cells (ASMCs). Therefore, mTOR and its mediated signaling network have become a new research hotspot in asthma airway remodeling in recent years. This article reviews the molecular mechanisms of mTOR in regulating asthma airway remodeling from the perspective of signal targets such as PIK3/AKT, AMPK, and NF-κB, providing a theoretical basis for the study of asthma airway remodeling mechanisms and the development of new drugs.