Phenotype and functional plasticity of airway smooth muscle: role of caveolae and caveolins.
Phenotype and functional plasticity of airway smooth muscle: role of caveolae and caveolins.
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DOI：
10.1513/pats.200705-057vs
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Gosens, Reinoud
中科院分区：
文献类型：
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作者：
Halayko, Andrew J;Tran, Thai;Gosens, Reinoud
气道平滑肌（ASM）细胞表现出表型可塑性，这是在外部刺激，如生长因子和细胞外基质的控制下，并通过细胞内信号级联网络控制表型特异性基因的转录和蛋白质翻译。表型可塑性支持气道肌细胞导致急性支气管痉挛和慢性哮喘气道重塑特征的能力。成熟的收缩性ASM细胞的一个特征是存在丰富的小窝，欧米茄形质膜内陷，其由脂筏与小窝蛋白-1（一种具有结构和功能特性的独特蛋白质）的结合发展而来。Caveolae和Caveolin-1调节来自生长因子和收缩激动剂受体的信号传导，因此可以调节肌细胞的功能多样性。小窝蛋白-1似乎在ASM细胞增殖中起抑制作用，并协调受体介导的信号转导，调节ASM细胞的表型表达。有趣的是，在收缩肌细胞小窝组织在细胞内钙离子处理细胞器附近，并划分成离散的线性结构域与β-肌营养不良蛋白聚糖，肌动蛋白拴系的肌营养不良蛋白糖蛋白复合物（DGC）的亚基对齐。尽管开发了转基因模型来研究小窝蛋白生物学，但对这些蛋白质在ASM表型表达和特定表型的肌细胞功能反应的调节中的作用只有肤浅的了解。本文综述了调节ASM细胞表型可塑性的机制，以及小窝作为特定表型状态ASM细胞功能多样性的决定因素的作用。
Airway smooth muscle (ASM) cells exhibit phenotype plasticity that is under control of external stimuli such as growth factors and the extracellular matrix, and is regulated by a network of intracellular signaling cascades that control transcription and protein translation of phenotype-specific genes. Phenotype plasticity underpins the ability of airway myocytes to contribute both to acute bronchospasm, and to the features of airway remodeling in chronic asthma. A feature of mature, contractile ASM cells is the presence of abundant caveolae, omega-shaped plasma membrane invaginations that develop from the association of lipid rafts with caveolin-1, a unique protein with structural and functional properties. Caveolae and caveolin-1 modulate signaling from receptors for growth factors and contractile agonists, and thus may modulate functional diversity of myocytes. Caveolin-1 appears to play a suppressive role in ASM cell proliferation, and orchestrates receptor-mediated signal transduction that regulates phenotype expression of ASM cells. Interestingly, in contractile myocytes caveolae are organized in close proximity to intracellular Ca2+-handling organelles, and are partitioned into discrete linear domains aligned with beta-dystroglycan, a subunit of the actin-tethered dystrophin glycoprotein complex (DGC). Despite development of transgenic models to investigate caveolin biology, only superficial understanding of the role of these proteins in ASM phenotype expression and modulation of the functional responses of myocytes of a particular phenotype is available. This review summarizes mechanisms regulating ASM cell phenotype plasticity, and the role of caveolae as determinants of the functional diversity of ASM cells of a particular phenotypic state.