Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Esophagus
Published in: Esophagus 2/2017

01-04-2017 | Original Article

Epidermal differentiation complex protein involucrin is down-regulated in eosinophilic esophagitis

Authors: Naoki Oshima, Shunji Ishihara, Nobuhiko Fukuba, Yoshiyuki Mishima, Kousaku Kawashima, Norihisa Ishimura, Noriyoshi Ishikawa, Riruke Maruyama, Yoshikazu Kinoshita

Published in: Esophagus | Issue 2/2017

Login to get access

Abstract

Background and aims

Epidermal differential complex (EDC) proteins, such as filaggrin, involucrin, and loricrin, play key roles to protect the mucosal surface against invading pathogens. Eosinophilic esophagitis (EoE) is an allergic gastrointestinal disease that features eosinophilic infiltration of esophageal mucosa, though the function of EDC proteins in its pathogenesis remains unknown. The aim of this study was to investigate possible differences of EDC protein expression in the epithelium of the esophagus, pharynx, and tongue. Furthermore, we examined that expression in esophageal specimens obtained from patients with EoE.

Methods

For evaluating EDC protein expression in epithelium from different locations, we enrolled 72 patients who underwent surgical resection for esophageal, pharyngeal, or tongue squamous cell carcinoma. Pathological samples were used for analysis of expression by immunohistochemistry. In addition, samples were obtained from 10 patients with EoE and 11 healthy subjects, and compared for esophageal epithelial expression of EDC proteins.

Results

In epithelium samples obtained from the esophagus, pharynx, and tongue, the presence of EDC proteins was confirmed by immunohistochemistry analysis findings, though the expression patterns were notably different in comparison to that in epidermis samples. In EoE patients, the expression of involucrin was dramatically down-regulated in esophageal mucosa, whereas down-regulation of filaggrin and loricrin did not reach a statistically significant level.

Conclusion

EDC protein expression was clearly detected in pharyngoesophageal epithelium samples, while that of involucrin alone was markedly reduced in patients with EoE.
Literature
1.
Asher MI, Montefort S, Björkstén B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet. 2006;368(9537):733–43.CrossRefPubMed
2.
Wesemann DR, Nagler CR. The Microbiome, timing, and barrier function in the context of allergic disease. Immunity. 2016;44(4):728–38.CrossRefPubMed
3.
Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005;6(4):328–40.CrossRefPubMed
4.
Kypriotou M, Huber M, Hohl D. The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the ‘fused genes’ family. Exp Dermatol. 2012;21(9):643–9.CrossRefPubMed
5.
6.
Eckert RL, Crish JF, Efimova T, et al. Regulation of involucrin gene expression. J Invest Dermatol. 2004;123(1):13–22.CrossRefPubMed
7.
Iizuka H, Takahashi H, Honma M, Ishida-Yamamoto A. Unique keratinization process in psoriasis: late differentiation markers are abolished because of the premature cell death. J Dermatol. 2004;31(4):271–6.CrossRefPubMed
8.
Marenholz I, Volz A, Ziegler A, et al. Genetic analysis of the epidermal differentiation complex (EDC) on human chromosome 1q21: chromosomal orientation, new markers, and a 6-Mb YAC contig. Genomics. 1996;37(3):295–302.CrossRefPubMed
9.
Kinoshita Y, Furuta K, Ishimaura N, et al. Clinical characteristics of Japanese patients with eosinophilic esophagitis and eosinophilic gastroenteritis. J Gastroenterol. 2013;48(3):333–9.CrossRefPubMed
10.
11.
Kinoshita Y, Ishimura N, Oshima N, et al. Recent progress in the research of eosinophilic esophagitis and gastroenteritis. Digestion. 2016;93(1):7–12.CrossRefPubMed
12.
13.
Ishimura N, Furuta K, Sato S, Ishihara S, Kinoshita Y. Limited role of allergy testing in patients with eosinophilic gastrointestinal disorders. J Gastroenterol Hepatol. 2013;28(8):1306–13.CrossRefPubMed
14.
Ishimura N, Shimura S, Jiao D, et al. Clinical features of eosinophilic esophagitis: differences between Asian and Western populations. J Gastroenterol Hepatol. 2015;30(Suppl 1):71–7.CrossRefPubMed
15.
Simon D, Radonjic-Hosli S, Straumann A, Yousefi S, Simon HU. Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy. 2015;70(4):443–52.CrossRefPubMed
16.
Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116(2):536–47.CrossRefPubMedPubMedCentral
17.
Blanchard C, Stucke EM, Burwinkel K, et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010;184(7):4033–41.CrossRefPubMed
18.
Wawrzyniak P, Akdis CA, Finkelman FD, Rothenberg ME. Advances and highlights in mechanisms of allergic disease in 2015. J Allergy Clin Immunol. 2016;137(6):1681–96.CrossRefPubMed
19.
Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118(1):214–9.CrossRefPubMed
20.
Palmer CN, Irvine AD, Terron-Kwiatkowski A, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441–6.CrossRefPubMed
21.
Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14):1315–27.CrossRefPubMed
22.
Jiao D, Ishimura N, Maruyama R, et al. Similarities and differences among eosinophilic esophagitis, proton-pump inhibitor-responsive esophageal eosinophilia, and reflux esophagitis: comparisons of clinical, endoscopic, and histopathological findings in Japanese patients. J Gastroenterol. 2016. doi:10.​1007/​s00535-016-1213-1.PubMed
23.
24.
Kim BE, Howell MD, Guttman-Yassky E, et al. TNF-alpha downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-alpha antagonists to improve skin barrier. J Invest Dermatol. 2011;131(6):1272–9.CrossRefPubMed
25.
McAleer MA, Irvine AD. The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol. 2013;131(2):280–91.CrossRefPubMed
26.
Jiang M, Ku WY, Zhou Z, et al. BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis. J Clin Invest. 2015;125(4):1557–68.CrossRefPubMedPubMedCentral
27.
Shoda T, Morita H, Nomura I, et al. Comparison of gene expression profiles in eosinophilic esophagitis (EoE) between Japan and Western countries. Allergol Int. 2015;64(3):260–5.CrossRefPubMed
Metadata
Title
Epidermal differentiation complex protein involucrin is down-regulated in eosinophilic esophagitis
Authors
Naoki Oshima
Shunji Ishihara
Nobuhiko Fukuba
Yoshiyuki Mishima
Kousaku Kawashima
Norihisa Ishimura
Noriyoshi Ishikawa
Riruke Maruyama
Yoshikazu Kinoshita
Publication date
01-04-2017
Publisher
Springer Japan
Published in
Esophagus / Issue 2/2017
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-016-0568-y

Other articles of this Issue 2/2017

Esophagus 2/2017 Go to the issue

Original Article

Effects of acotiamide on esophageal motility in healthy subjects: a randomized, double-blind, placebo-controlled crossover study

Original Article

Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus

Case Report

Relaxing incision of the diaphragm for esophageal hiatal closure for giant paraesophageal hiatal hernia

Original Article

Hand-assisted technique beneficial for laparoscopic transhiatal esophagectomy with en-bloc dissection of middle and lower mediastinal lymph nodes: roles of the operator’s left hand

Original Article

Establishment of a DEN-induced mouse model of esophageal squamous cell carcinoma metastasis

Review Article

Optimal acid suppressive treatment for adequate symptom relief and prevention of the complications of gastroesophageal reflux disease: differences in long-term clinical course and pathophysiology among disease subtypes
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits