Rogers Duncan F
Thoracic Medicine, National Heart and Lung Institute (Imperial College), Dovehouse Street, London, SW3 6LY, UK.
Int J Biochem Cell Biol. 2003 Jan;35(1):1-6. doi: 10.1016/s1357-2725(02)00083-3.
The two principal features of airway goblet cells are rapid secretion of mucin onto the airway surface and increase in number (hyperplasia) with chronic inhaled 'insult'. The first is associated with homeostasis, the latter with pathophysiology. Myristoylated alanine-rich C kinase (MARCKS) is a key molecule regulating mucin exocytosis, a process also involving cooperative interaction between protein kinase (PK) C and PKG. The epidermal growth factor (EGF) cascade and calcium activated chloride channels (CLCA) are key signalling molecules involved in development of goblet cell hyperplasia, with Bcl-2, an inhibitor of apoptosis, involved in maintenance of hyperplasia. Goblet cell hyperplasia and associated mucus hypersecretion is a pathophysiological feature of asthma and chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies to prevent or reverse goblet cell hyperplasia include inhibitors of EGF receptor tyrosine kinase and CLCA, of which viable pharmaceutical molecules are now available for clinical trial in hypersecretory conditions of the airways.
气道杯状细胞的两个主要特征是将黏蛋白快速分泌到气道表面以及随着慢性吸入“刺激”而数量增加（增生）。第一个特征与内环境稳定有关，第二个特征与病理生理学有关。肉豆蔻酰化富含丙氨酸的蛋白激酶C（MARCKS）是调节黏蛋白胞吐作用的关键分子，这一过程还涉及蛋白激酶（PK）C和蛋白激酶G（PKG）之间的协同相互作用。表皮生长因子（EGF）级联反应和钙激活氯离子通道（CLCA）是参与杯状细胞增生发展的关键信号分子，而凋亡抑制剂Bcl-2则参与增生的维持。杯状细胞增生及相关的黏液分泌过多是哮喘和慢性阻塞性肺疾病（COPD）的病理生理特征。预防或逆转杯状细胞增生的新型治疗策略包括EGF受体酪氨酸激酶和CLCA的抑制剂，其中一些可行的药物分子现已可用于气道分泌过多疾病的临床试验。
