Li Xin, Jin Fengri, Lee Hyun Jae, Lee Choong Jae
Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University, Seoul 01795, Republic of Korea.
Biomol Ther (Seoul). 2021 May 1;29(3):303-310. doi: 10.4062/biomolther.2020.149.
In the present study, kaempferol, a flavonoidal natural compound found in Polygonati Rhizoma, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. A human respiratory epithelial NCI-H292 cells was pretreated with kaempferol for 30 min and stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway or EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Kaempferol suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IκBα), and NF-κB p65 nuclear translocation. Also, kaempferol inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest kaempferol regulates the gene expression and production of mucin through regulation of NF-κB and MAPK signaling pathways, in human airway epithelial cells.
在本研究中，对黄精中发现的黄酮类天然化合物山奈酚对气道MUC5AC粘蛋白的基因表达和产生的潜在影响进行了研究。用人呼吸道上皮NCI-H292细胞用山奈酚预处理30分钟，然后在接下来的24小时内用表皮生长因子（EGF）或佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）刺激。研究了对PMA诱导的核因子κB（NF-κB）信号通路或EGF诱导的丝裂原活化蛋白激酶（MAPK）信号通路的影响。山奈酚通过抑制抑制性κBα（IκBα）的降解和NF-κB p65核转位，抑制了PMA诱导的MUC5AC粘蛋白的产生和基因表达。此外，山奈酚通过调节表皮生长因子受体（EGFR）的磷酸化、p38丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶（ERK）1/2（p44/42）的磷酸化以及特异性蛋白-1（Sp1）的核表达，抑制了EGF诱导的MUC5AC粘蛋白的基因表达和产生。这些结果表明，山奈酚在人气道上皮细胞中通过调节NF-κB和MAPK信号通路来调节粘蛋白的基因表达和产生。
