Stewart A G
Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
Pulm Pharmacol Ther. 2001;14(3):255-65. doi: 10.1006/pupt.2001.0290.
Airway wall remodelling contributes to the airway hyperresponsiveness that characterizes asthma. An increase in airway smooth muscle (ASM) volume is quantitatively important in the overall remodelling response and may be considered as a target for new therapeutic approaches to chronic asthma. ASM volume increases result from both hypertrophic as well as hyperplastic growth, the latter having been more extensively investigated. There are relatively few in vivo models available for analysis of the underlying mechanism(s) or their regulation by drugs. Human ASM in culture has been used to investigate potential stimuli for ASM proliferation and the signal transduction pathways that subserve these responses. The mitogen-activated protein kinase (MAPK) family members, ERK 1/2 and the phosphoinositol-3-kinase (PI3K) pathways each contribute to the signalling of G1 progression/S-phase entry in ASM. Glucocorticoids and beta(2)-adrenoceptor agonists attenuate, but do not prevent proliferative responses of ASM. Thus, there is scope for improved pharmacological control of this chronic and progressive aspect of asthma pathogenesis.
气道壁重塑会导致气道高反应性，这是哮喘的一个特征。气道平滑肌（ASM）体积增加在整体重塑反应中具有重要的定量意义，可被视为慢性哮喘新治疗方法的一个靶点。ASM体积增加是由肥大性生长和增生性生长共同导致的，后者已得到更广泛的研究。目前用于分析潜在机制或药物对其调控的体内模型相对较少。培养的人ASM已被用于研究ASM增殖的潜在刺激因素以及介导这些反应的信号转导途径。丝裂原活化蛋白激酶（MAPK）家族成员ERK 1/2和磷酸肌醇-3-激酶（PI3K）途径均参与ASM中G1期进展/进入S期的信号传导。糖皮质激素和β2肾上腺素能受体激动剂可减弱但不能阻止ASM的增殖反应。因此，在哮喘发病机制的这一慢性和进展性方面，改善药物控制仍有空间。
