Dual ERK and phosphatidylinositol 3-kinase pathways control airway smooth muscle proliferation: Differences in asthma

摘要: Hyperplasia of airway smooth muscle (ASM) within the bronchial wall asthmatic patients has been well documented and is likely due to increased proliferation. We have shown that ASM cells obtained from proliferate faster than those non-asthmatic patients. In non-asthmatics, mitogens act via dual signaling pathways (both ERK- PI 3-kinase-dependent) control growth. this study we are first examine whether enhanced proliferation asthmatics. When were incubated with 0.1% or 1% FBS, ERK activation was significantly greater in subjects (P < 0.05). contrast, when stimulated 10% activity cells. However, cell still higher by both FBS. Pharmacological inhibition revealed although proliferative growth non-asthmatics FBS an equal extent ([(3)H]-thymidine incorporation reduced 57.2 +/- 6.9% 3-kinase inhibitor LY294002 57.8 1.1% ERK-pathway U0126); asthmatics, presence a strong stimulus (10% FBS) reduces resulting shift pathway. The underlying mechanism appears be upregulation endogenous MAPK inhibitor--MKP-1--that constrains under mitogenic stimulation. This suggests pathway may attractive target for reversing hyperplasia asthma.