Song Won-Yong, Song Yong-Seok, Ryu Hyung Won, Oh Sei-Ryang, Hong JinTae, Yoon Do-Young
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea.
J Microbiol Biotechnol. 2017 Jan 28;27(1):49-56. doi: 10.4014/jmb.1610.10012.
In the human airway, mucus exists to protect the respiratory system as a primary barrier of the innate immune system. However, hyperexpressed mucus limits airflow, resulting in a decrease of lung function. Among more than 20 mucin family members, MUC5AC and MUC5B are major glycoproteins in human airway mucus. The epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression. Even though there are some drugs for treating mucus hypersecretion, no drug has proven effects on humans. We found that the flavonoid tilianin regulated MUC5AC expression and also inhibited Sp1 phosphorylation. In this study, we investigated how tilianin would modulate EGFR signaling and regulate mucin production. In conclusion, tilianin inhibited MUC5AC expression mediated via modulating the EGFRMEK-ERK-Sp1 signaling pathway in NCI-H292 human airway epithelial cells. This study may provide the basis for the novel treatment of mucus hypersecretion.
在人类气道中，黏液作为先天性免疫系统的主要屏障，起着保护呼吸系统的作用。然而，黏液过度分泌会限制气流，导致肺功能下降。在20多种黏蛋白家族成员中，MUC5AC和MUC5B是人类气道黏液中的主要糖蛋白。表皮生长因子受体（EGFR）信号通路是这些黏蛋白表达的机制之一，特异性蛋白-1（Sp1）转录因子是该通路的下游信号，在黏蛋白表达中起关键作用。尽管有一些治疗黏液分泌过多的药物，但尚无药物被证实对人类有效。我们发现黄酮类化合物田蓟苷可调节MUC5AC的表达，并抑制Sp1磷酸化。在本研究中，我们研究了田蓟苷如何调节EGFR信号并调控黏蛋白的产生。总之，田蓟苷通过调节NCI-H292人气道上皮细胞中的EGFR-MEK-ERK-Sp1信号通路，抑制了MUC5AC的表达。本研究可能为黏液分泌过多的新型治疗提供依据。
