Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.149
Kaempferol Regulates the Expression of Airway MUC5AC Mucin Gene via IκBα-NF-κB p65 and p38-p44/42-Sp1 Signaling Pathways
Xin Li1†, Fengri Jin1†, Hyun Jae Lee2* and Choong Jae Lee1*
1Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon 35015,
2Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University, Seoul 01795, Republic of Korea
*E-mail: hjy1213@syu.ac.kr (Lee HJ), LCJ123@cnu.ac.kr (Lee CJ)
Tel: +82-2-3399-1909 (Lee HJ), +82-42-580-8255 (Lee CJ)
Fax: +82-2-3399-1909 (Lee HJ), +82-42-585-6627 (Lee CJ)
The first two authors contributed equally to this work.
Received: August 25, 2020; Revised: November 11, 2020; Accepted: November 12, 2020; Published online: December 7, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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.
Keywords: MUC5AC, Pulmonary mucin, Kaempferol


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