Hasaneen Nadia A, Zucker Stanley, Cao Jian, Chiarelli Christian, Panettieri Reynold A, Foda Hussein D
Department of Medicine and Research, VAMC Northport, Northport, New York, USA.
FASEB J. 2005 Sep;19(11):1507-9. doi: 10.1096/fj.04-3350fje. Epub 2005 Jul 13.
Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.
气道平滑肌（ASM）的增殖和迁移是哮喘气道重塑的主要组成部分。哮喘气道会受到机械牵张，这有助于其重塑。基质金属蛋白酶（MMP）在重塑过程中起重要作用。在本研究中，我们检测了人ASM（HASM）细胞的机械牵张是否会促进其增殖和迁移以及MMP在此过程中的作用。使用FlexCell系统对HASM施加机械牵张。评估HASM细胞的增殖、迁移以及MMP的释放、激活和表达。我们的结果表明，周期性牵张增加了HASM的增殖和迁移；周期性牵张增加了MMP-1、-2和-3以及膜型1-MMP的释放和激活；MMP释放之前细胞外MMP诱导剂增加；普林司他[一种MMP抑制剂（MMPI）]显著降低了周期性牵张诱导的HASM增殖和迁移；并且牵张诱导的MMP释放增加伴随着肌腱蛋白-C释放增加。总之，周期性机械牵张在HASM细胞增殖和迁移中起重要作用。这种增殖和迁移的增加是通过MMP释放和激活的增加实现的。在寻求哮喘气道重塑的治疗选择时应考虑使用药理MMPI。
