Stewart Alastair G, Bonacci John V, Quan Lilly
Department of Pharmacology, University of Melbourne, Grattan Street, Victoria, Australia 3010.
Curr Allergy Asthma Rep. 2004 Mar;4(2):109-15. doi: 10.1007/s11882-004-0055-8.
Airway smooth muscle proliferation has been the focus of considerable attention, as it is a quantitatively important component of the airway wall remodeling response in asthma and has been suggested as a suitable target for the development of novel anti-asthma agents. Such agents are considered likely to reduce airway hyperresponsiveness and, consequently, airway obstruction, resulting in fewer symptoms and exacerbations. Identifying suitable drug targets has proved an elusive goal, as no dominant molecular mechanism for remodeling has emerged. Moreover, recent findings raise some doubt as to whether smooth muscle proliferation per se is the explanation of the increase in smooth muscle cell number in asthma, with alternative explanations including the proposal that cells migrate either from the interstitial compartment or from a circulating precursor stem cell population. Therefore, drug targeting of migration responses should be considered as an alternative approach to regulating the smooth muscle component of airway wall remodeling.
气道平滑肌增殖一直是备受关注的焦点,因为它是哮喘气道壁重塑反应中一个在数量上很重要的组成部分,并且已被认为是开发新型抗哮喘药物的合适靶点。这类药物被认为有可能降低气道高反应性,进而减少气道阻塞,从而减轻症状和发作次数。事实证明,确定合适的药物靶点是一个难以实现的目标,因为尚未出现主导重塑过程的分子机制。此外,最近的研究结果对平滑肌增殖本身是否能解释哮喘中平滑肌细胞数量的增加提出了一些疑问,其他解释包括细胞从间质区或循环前体干细胞群体迁移的说法。因此,针对迁移反应的药物靶向治疗应被视为调节气道壁重塑平滑肌成分的一种替代方法。