Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei, Taiwan.
Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
J Cell Mol Med. 2024 Apr;28(8):e18299. doi: 10.1111/jcmm.18299.
Pulmonary fibrosis is a lung disorder affecting the lungs that involves the overexpressed extracellular matrix, scarring and stiffening of tissue. The repair of lung tissue after injury relies heavily on Type II alveolar epithelial cells (AEII), and repeated damage to these cells is a crucial factor in the development of pulmonary fibrosis. Studies have demonstrated that chronic exposure to PM2.5, a form of air pollution, leads to an increase in the incidence and severity of pulmonary fibrosis by stimulation of epithelial-mesenchymal transition (EMT) in lung epithelial cells. Pyrroloquinoline quinone (PQQ) is a bioactive compound found naturally that exhibits potent anti-inflammatory and anti-oxidative properties. The mechanism by which PQQ prevents pulmonary fibrosis caused by exposure to PM2.5 through EMT has not been thoroughly discussed until now. In the current study, we discovered that PQQ successfully prevented PM2.5-induced pulmonary fibrosis by targeting EMT. The results indicated that PQQ was able to inhibit the expression of type I collagen, a well-known fibrosis marker, in AEII cells subjected to long-term PM2.5 exposure. We also found the alterations of cellular structure and EMT marker expression in AEII cells with PM2.5 incubation, which were reduced by PQQ treatment. Furthermore, prolonged exposure to PM2.5 considerably reduced cell migratory ability, but PQQ treatment helped in reducing it. In vivo animal experiments indicated that PQQ could reduce EMT markers and enhance pulmonary function. Overall, these results imply that PQQ might be useful in clinical settings to prevent pulmonary fibrosis.
肺纤维化是一种影响肺部的肺部疾病，涉及细胞外基质的过度表达、组织的瘢痕形成和僵硬。肺组织损伤后的修复严重依赖于 II 型肺泡上皮细胞 (AEII)，而这些细胞的反复损伤是肺纤维化发展的关键因素。研究表明，慢性暴露于 PM2.5（一种空气污染形式）会通过刺激肺上皮细胞的上皮-间充质转化 (EMT) 导致肺纤维化的发病率和严重程度增加。吡咯喹啉醌 (PQQ) 是一种天然存在的生物活性化合物，具有强大的抗炎和抗氧化特性。直到现在，PQQ 通过 EMT 防止 PM2.5 暴露引起的肺纤维化的机制仍未得到充分讨论。在目前的研究中，我们发现 PQQ 通过靶向 EMT 成功预防了 PM2.5 引起的肺纤维化。结果表明，PQQ 能够抑制长期暴露于 PM2.5 的 AEII 细胞中 I 型胶原的表达，I 型胶原是一种众所周知的纤维化标志物。我们还发现，用 PM2.5 孵育 AEII 细胞会改变细胞结构和 EMT 标志物的表达，而 PQQ 处理则会减少这些变化。此外，长期暴露于 PM2.5 会大大降低细胞迁移能力，但 PQQ 处理有助于降低这种能力。体内动物实验表明，PQQ 可以降低 EMT 标志物并增强肺功能。总的来说，这些结果表明 PQQ 可能在临床上用于预防肺纤维化。
