Effect of Epigallocatechin-3-Gallate on PMA-Induced MUC5B Expression in Human Airway Epithelial Cells

Song, Eun Jung; Bae, Chang Hoon; Kim, Jong-Yeon; Kim, Yong-Woon; Park, Soyoung; Song, Si-Youn; Kim, Yong‐Dae

doi:10.3342/ceo.2013.6.4.237

Cited by 11 publications

(10 citation statements)

References 18 publications

(24 reference statements)

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“…The components of this pathway that have been specifically implicated in MUC5B regulation include p38 MAPK, ERK, NF-κB, MMP-9, ROS, RSK1, CREB, IL-1β, and IL-17A [157,305,309,312,[315][316][317][319][320][321]. This pathway is undoubtedly contributing to the regulation/dysregulation of MUC5B, likely acting through a proximal promoter [322].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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Idiopathic pulmonary fibrosis (IPF) is the most common and the most aggressive fibrosing interstitial lung disease (ILD). Despite recent promising clinical trials, IPF remains incurable and largely untreatable. Genetic studies have identified several risk loci for both sporadic and familial forms of IPF. A single variant upstream of MUC5B is predicted to account for more than 30% of all IPF risk. This variant, rs35705950, is associated with expression of MUC5B in healthy lung tissue. However, the mechanism underlying the relationship between rs35705950 and MUC5B expression remains unclear.The first goal of my thesis research was to determine whether rs35705950 is also a risk factor for other forms of ILD. Genomic DNA from individuals with IPF, HP, COPD, iNSIP, and RB-ILD was obtained and genotyped for the common MUC5B promoter variant. In these populations the risk allele was associated with IPF and iNSIP which suggested a potential shared disease mechanism. Additionally, I showed that in the IPF and control populations rs35705950 is associated with lung MUC5B expression.The second goal of my thesis research was to investigate MUC5B promoter DNA methylation which has previously been shown to play a role in MUC5B expression.Methylation analysis of the 4KB region upstream of MUC5B identified two differentially methylated regions (DMRs) associated with IPF, one DMR associated with MUC5B iv expression, and one DMR associated with rs35705950. The IPF, MUC5B expression, and rs35705950 associated DMRs are all differentially methylated at a cluster of 11 CpG motifs. overlapping DMR, including the motif disrupted by rs35705950. These findings suggest that DNA methylation may play a role in MUC5B gene regulation and IPF risk.Next, I used cross species analysis to identify highly conserved domains within the overlapping DMR. Evolutionary conservation indicated selective pressures to maintain sequences overtime and suggests biological importance. The overlapping DMR contains a highly conserved binding motif for FOXA2, a transcription factor. Further analysis using ChIP-qPCR, reporter constructs, and siRNA, established a role for FOXA2 in regulation of MUC5B expression in lung tissue. Additionally, siRNA knock down identified 3 other transcription factors which are associated with MUC5B expression; STAT3, HOXA9 and ZBTB7A. These transcriptional regulators provide insight into possible therapeutic intervention for MUC5B dysregulation and IPF.The form and content of this abstract are approved. I recommend its publication.

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Section: Introductionmentioning

confidence: 99%

“…Lastly, epigallocatechin-3-gallate, a major component of green tea extract, inhibits the stimulation of MUC5B expression [319] and TGF-β(2) reportedly decreased MUC5B expression [311].…”

Section: Introductionmentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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“…After incubation, the gel was stained by 0.5% Coomassie Blue R‐250 (Bio‐Rad Laboratories, Hercules, CA) and destained in 30% methanol and 5% acetic acid solution, and then rinsed to visualize the digested bands in the gelatin matrix. The gels were photographed and the average band intensity was measured using a commercially available imaging software (Scion Corporation, Frederick, MD) 23 …”

Section: Methodsmentioning

confidence: 99%

“…The gels were photographed and the average band intensity was measured using a commercially available imaging software (Scion Corporation, Frederick, MD). 23…”

Section: Gelatin Zymographymentioning

confidence: 99%

Pepsin exposure in a non‐acidic environment upregulates mucin 5AC (MUC5AC) expression via matrix metalloproteinase 9 (MMP9)/nuclear factor κB (NF‐κB) in human airway epithelial cells

Choi

Bae

et al. 2020

Int Forum Allergy Rhinol

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Background Gastric reflux GR is a backflow of gastric content to the aerodigestive tract GR was previously found to be associated with inflammatory airway diseases and a potential cause of airway remodeling Chronic exposure to gastric content may induce damage from nose to lung because digestive enzymes and acidity are toxic to airway epithelial cells Recently the toxicity of pepsin in a non-acidic environment was found to increase proinflammatory cytokines and receptors in the epithelium of the aerodigestive tract However the effect of pepsin in non-acidic conditions on mucin expression has not been investigated in human airway epithelial cells The purpose of this study was to evaluate the effect of pepsin on mucin AC MUC AC expression in upper and lower airway epithelial cells as an important potential factor of non-acidic GR-related airway inflammation Methods In NCI-H cells and human nasal epithelial cells HNEpCs the effects and signaling pathways of pepsin on MUC AC expression were examined using reverse-transcription polymerase chain reaction RT-PCR real-time PCR enzyme immunoassay zymography Western blot and immunofluorescence staining ResultsPepsin increased MUC AC expression in non-acidic condition of NCI-H cells and HNEpCs Further pepsin activated matrix metalloproteinase MMP and phosphorylated nuclear factor κB NF-κB Moreover inhibitors of MMP and NF-κB significantly attenuated pepsin-induced MUC AC expression and the knockdown of NF-κB by small interfering RNA siRNA significantly blocked pepsin-induced MUC AC expression in human airway epithelial cells Conclusion These findings suggest that pepsin increased MUC AC expression in non-acidic conditions via the activation of MMP and NF-κB in human airway epithelial cells

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“…Therefore, many animal studies related to EGCG, including our own, were performed in the concentration range of 3-20 mg/kg/day, which is likely to be achieved under physiologic condition and is not expected to cause any negative side effects (8,9,21,22) . Previous in vitro studies of EGCG on airway epithelial cell, the concentration range of 10-1000 µM was used, because topical application of EGCG on nasal mucosa might achieve the effective experimental dosage of EGCG, allowing the use of EGCG as a therapeutic agent (6,10,23) .…”

Section: Egcg Inhibits Mmp-9 and Muc5b Expression In The Nasal Epithementioning

confidence: 99%