JNJ0966 inhibits PDGF-BB-induced airway smooth muscle cell proliferation and extracellular matrix production by regulating MMP-9

Abstract

The increased proliferation and extracellular matrix (ECM) production of airway smooth muscle cells (ASMCs) are crucial factors in asthma progression. JNJ0966, one of the metalloproteinase-9 (MMP-9)-specific inhibitors, has been demonstrated to be involved in the progression and development of diversified diseases. Nevertheless, the function of JNJ0966 in ASMCs remains unclear. This study aimed at investigating the effects of JNJ0966 on asthma progression. In our study, the platelet-derived growth factor BB (PDGF-BB) was first utilized to stimulate the cell model for asthma. Results demonstrated that the cell viability of ASMCs was increased by PDGF-BB (0, 10, 20, and 30 ng/mL) in a dose-dependent manner. Further investigation revealed that JNJ0966 inhibited the cell activity and migration ability of PDGF-BB-induced ASMCs. In addition, JNJ0966 relieved ECM deposition in PDGF-BB-induced ASMCs. Finally, through rescue assays, the results showed that overexpression of MMP-9 reversed the inhibitory effects of JNJ0966 on cell viability and ECM deposition in ASMCs. In conclusion, our findings suggested that JNJ0966 inhibited PDGF-BB-induced ASMC proliferation and ECM production by modulating MMP-9. These findings might provide novel insight for the treatment of asthma.