Department of Tuberculosis, The Sixth People's Hospital of Nantong, Nantong, Jiangsu Province, 226000, China.
Department of Tuberculosis, The Sixth People's Hospital of Nantong, Nantong, Jiangsu Province, 226000, China;
Allergol Immunopathol (Madr). 2022 Jul 1;50(4):57-63. doi: 10.15586/aei.v50i4.610. eCollection 2022.
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.
气道平滑肌细胞（ASMCs）的增殖和细胞外基质（ECM）的产生增加是哮喘进展的关键因素。金属蛋白酶-9（MMP-9）特异性抑制剂 JNJ0966 已被证明参与了多种疾病的进展和发展。然而，JNJ0966 在 ASMCs 中的功能仍不清楚。本研究旨在探讨 JNJ0966 对哮喘进展的影响。在我们的研究中，首先利用血小板衍生生长因子 BB（PDGF-BB）刺激哮喘细胞模型。结果表明，PDGF-BB（0、10、20 和 30ng/mL）呈剂量依赖性地增加 ASMCs 的细胞活力。进一步的研究表明，JNJ0966 抑制了 PDGF-BB 诱导的 ASMCs 的细胞活性和迁移能力。此外，JNJ0966 缓解了 PDGF-BB 诱导的 ASMCs 中的 ECM 沉积。最后，通过挽救实验，结果表明 MMP-9 的过表达逆转了 JNJ0966 对 ASMCs 细胞活力和 ECM 沉积的抑制作用。总之，我们的研究结果表明，JNJ0966 通过调节 MMP-9 抑制 PDGF-BB 诱导的 ASMC 增殖和 ECM 产生。这些发现可能为哮喘的治疗提供新的思路。
