Emodin Inhibited MUC5AC Mucin Gene Expression Via Affecting EGFR-MAPK-Sp1 Signaling Pathway in Human Airway Epithelial Cells

Overview

Journal Biomol Ther (Seoul)

Specialty Pharmacology

Date 2024 Oct 20

PMID 39428383

Authors

Rajib Hossain

Hyun Jae Lee

Chang-Heon Baek

Sun-Chul Hwang

Choong Jae Lee

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to evaluate emodin, a natural trihydroxyanthraquinone compound found in the roots and barks of several plants including rhubarb and buckthorn, might attenuate epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. The human pulmonary mucoepidermoid NCI-H292 cells were pretreated with for 30 min and then stimulated with EGF for the following 24 h. The effect of emodin on EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was examined. As a result, emodin blocked the expression of MUC5AC mucin mRNA and production of mucous glycoprotein via suppressing the phosphorylation of EGF receptor (EGFR), phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1 and 2 (MEK1/2), phosphorylation of p38 MAPK, phosphorylation of ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings imply that emodin has a potential to mitigate EGF-stimulated mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway, in NCI-H292 cells.

References

Hossain R, Kim K, Li X, Lee H, Lee C . Involvement of IKK/IkBα/NF-kB p65 Signaling into the Regulative Effect of Engeletin on MUC5AC Mucin Gene Expression in Human Airway Epithelial Cells. Biomol Ther (Seoul). 2022; 30(5):473-478. PMC: 9424336. DOI: 10.4062/biomolther.2022.088. View

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S . PubChem 2023 update. Nucleic Acids Res. 2022; 51(D1):D1373-D1380. PMC: 9825602. DOI: 10.1093/nar/gkac956. View

Li X, Jin F, Lee H, Lee C . Recent Advances in the Development of Novel Drug Candidates for Regulating the Secretion of Pulmonary Mucus. Biomol Ther (Seoul). 2020; 28(4):293-301. PMC: 7327140. DOI: 10.4062/biomolther.2020.002. View

Shao M, Ueki I, Nadel J . Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A. 2003; 100(20):11618-23. PMC: 208807. DOI: 10.1073/pnas.1534804100. View

Hewson C, Edbrooke M, Johnston S . PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol. 2004; 344(3):683-95. DOI: 10.1016/j.jmb.2004.09.059. View

Tang L, Chen Q, Sun L, Zhu L, Liu J, Meng Z . Curcumin suppresses MUC5AC production via interfering with the EGFR signaling pathway. Int J Mol Med. 2018; 42(1):497-504. DOI: 10.3892/ijmm.2018.3609. View

Allinson J, Hardy R, Donaldson G, Shaheen S, Kuh D, Wedzicha J . The Presence of Chronic Mucus Hypersecretion across Adult Life in Relation to Chronic Obstructive Pulmonary Disease Development. Am J Respir Crit Care Med. 2015; 193(6):662-72. PMC: 4824943. DOI: 10.1164/rccm.201511-2210OC. View

Lee C, Jang J, Park G . α-Pinene Attenuates Methamphetamine-Induced Conditioned Place Preference in C57BL/6 Mice. Biomol Ther (Seoul). 2023; 31(4):411-416. PMC: 10315344. DOI: 10.4062/biomolther.2022.132. View

Chen X, Yang J, Shen H, Zhang X, Wang H, Wu G . Muc5ac Production Inhibited by Decreased lncRNA H19 via PI3K/Akt/NF-kB in Asthma. J Asthma Allergy. 2021; 14:1033-1043. PMC: 8373259. DOI: 10.2147/JAA.S316250. View

10.

Mann T, Larcombe A, Wang K, Shamsuddin D, Landwehr K, Noble P . Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract. Am J Physiol Lung Cell Mol Physiol. 2022; 322(5):L683-L698. DOI: 10.1152/ajplung.00487.2021. View

11.

Lemmon M, Schlessinger J . Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci. 1994; 19(11):459-63. DOI: 10.1016/0968-0004(94)90130-9. View

12.

Le Cras T, Acciani T, Mushaben E, Kramer E, Pastura P, Hardie W . Epithelial EGF receptor signaling mediates airway hyperreactivity and remodeling in a mouse model of chronic asthma. Am J Physiol Lung Cell Mol Physiol. 2011; 300(3):L414-21. PMC: 3064289. DOI: 10.1152/ajplung.00346.2010. View

13.

Kim J, Sikder M, Lee H, Rahman M, Kim J, Chang G . Phorbol ester or epidermal growth-factor-induced MUC5AC mucin gene expression and production from airway epithelial cells are inhibited by apigenin and wogonin. Phytother Res. 2012; 26(12):1784-8. DOI: 10.1002/ptr.4650. View

14.

. UniProt: the Universal Protein Knowledgebase in 2023. Nucleic Acids Res. 2022; 51(D1):D523-D531. PMC: 9825514. DOI: 10.1093/nar/gkac1052. View

15.

Ryu J, Kim K, Hossain R, Lee M, Hong J, Lee H . Meclofenamate Suppresses MUC5AC Mucin Gene Expression by Regulating the NF-kB Signaling Pathway in Human Pulmonary Mucoepidermoid NCI-H292 Cells. Biomol Ther (Seoul). 2023; 31(3):306-311. PMC: 10129850. DOI: 10.4062/biomolther.2023.035. View

16.

Lee S, Lee M, Kwak A, Lee J, Yoon G, Joo S . Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells. Biomol Ther (Seoul). 2023; 31(6):661-673. PMC: 10616518. DOI: 10.4062/biomolther.2023.155. View

17.

Tashiro E, Henmi S, Odake H, Ino S, Imoto M . Involvement of the MEK/ERK pathway in EGF-induced E-cadherin down-regulation. Biochem Biophys Res Commun. 2016; 477(4):801-806. DOI: 10.1016/j.bbrc.2016.06.138. View

18.

Ryu J, Lee H, Park S, Sikder M, Kim J, Hong J . Effect of Prunetin on TNF-α-Induced MUC5AC Mucin Gene Expression, Production, Degradation of IκB and Translocation of NF-κB p65 in Human Airway Epithelial Cells. Tuberc Respir Dis (Seoul). 2013; 75(5):205-9. PMC: 3861376. DOI: 10.4046/trd.2013.75.5.205. View

19.

Morris G, Huey R, Lindstrom W, Sanner M, Belew R, Goodsell D . AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16):2785-91. PMC: 2760638. DOI: 10.1002/jcc.21256. View

20.

Jang J, Yang G, Seok J, Kang H, Cho Y, Lee H . Loganin Prevents Hepatic Steatosis by Blocking NLRP3 Inflammasome Activation. Biomol Ther (Seoul). 2022; 31(1):40-47. PMC: 9810450. DOI: 10.4062/biomolther.2022.077. View