Original Article

Epithelial Barrier Function and Altered Cell Signaling Pathways in the Esophageal Epithelium of Achalasia Patients

Volume 37 · Issue 2 Publish Date: October 10, 2025
Sezgi Kipcak ORCID Pelin Ergun ORCID Nur Selvi Gunel ORCID Serhat Bor ORCID
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Turkish Journal of Gastroenterology

Volume 37 · Issue 2

Pages: 170-178

History

Published Online: October 10, 2025

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2025 Sezgi Kipcak, Pelin Ergun, Nur Selvi Gunel, Serhat Bor

Sezgi Kipcak ORCID
Department of Medical Biology, Ege University Medical School, Izmir, Türkiye
Pelin Ergun ORCID
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Wisconsin, USA
Nur Selvi Gunel ORCID
Department of Medical Biology, Ege University Medical School, Izmir, Türkiye
Serhat Bor ORCID
Division of Gastroenterology, Ege University Medical School, Izmir, Türkiye
Kipcak, S., Ergun, P., Gunel, N. S., & Bor, S. (2025). Epithelial Barrier Function and Altered Cell Signaling Pathways in the Esophageal Epithelium of Achalasia Patients. Turkish Journal of Gastroenterology, 37(2), 170–178. https://doi.org/10.5152/tjg.2025.25031
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Abstract

Background/Aims: Idiopathic achalasia is a rare esophageal motility disorder of unknown etiology. Although its neuromuscular aspects are well described, little is known about the role of the esophageal epithelium. This study aimed to evaluate the activation status of key cell signaling pathways and assess esophageal epithelial barrier function in achalasia patients.

Materials and Methods: Biopsy samples from 37 achalasia patients and 15 healthy volunteers (HVs) were analyzed. Tissue resistance and permeability were measured using a mini-Ussing chamber system. Gene expression related to epithelial integrity and signaling was assessed via quantitative reverse transcription polymerase chain reaction, and corresponding protein levels were evaluated using enzyme-linked immunosorbent assay (ELISA) and multiplex ELISA.

Results: No significant differences were observed in epithelial resistance (achalasia: 187.3 ± 25.6 Ω vs. HVs: 166.8 ± 20.1 Ω, P = .18) or permeability (achalasia: 35.76 ± 5.4 pmol vs. HVs: 36.9 ± 4.7 pmol, P = .67) between the 2 groups. Thirty-two genes involved in key sig
naling pathways were found to be significantly deregulated (P < .05), and 6 key signaling proteins (Akt (Ser473), c-Jun (Ser63), Erk1/2 (Th202/Tyr204), Thr185/Tyr187), IκB-α (Ser32/Ser36), MEK1 (Ser217/Ser221), mTOR (Ser2448)) were downregulated at the protein level (P < .05).

Conclusion: The findings reveal that major signaling pathways, including MAPK, PI3K/AKT/mTOR, and JAK/STAT, are significantly sup pressed in the esophageal epithelium of achalasia patients, despite preserved epithelial barrier integrity. These molecular alterations may represent a previously unrecognized component of achalasia pathogenesis. Furthermore, the preserved barrier function suggests that endoscopic therapies such as peroral endoscopic myotomy may not exacerbate reflux-related epithelial injury in these patients.

 

Cite this article as:Kipcak S, Ergun P, Gunel NS, Bor S. Epithelial barrier function and altered cell signaling pathways in the esophageal epithelium of achalasia patients. Turk J Gastroenterol. 2026;37(2):170-178.

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Article Info
Published In
Journal Turkish Journal of Gastroenterology
Volume / Issue Volume 37 · Issue 2
Pages 170-178
DOI 10.5152/tjg.2025.25031
History
Published Online October 10, 2025
License
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright
Copyright (c) 2025 Sezgi Kipcak, Pelin Ergun, Nur Selvi Gunel, Serhat Bor
Affiliations
Sezgi Kipcak ORCID
Department of Medical Biology, Ege University Medical School, Izmir, Türkiye
Pelin Ergun ORCID
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Wisconsin, USA
Nur Selvi Gunel ORCID
Department of Medical Biology, Ege University Medical School, Izmir, Türkiye
Serhat Bor ORCID
Division of Gastroenterology, Ege University Medical School, Izmir, Türkiye
Cite this Article
Kipcak, S., Ergun, P., Gunel, N. S., & Bor, S. (2025). Epithelial Barrier Function and Altered Cell Signaling Pathways in the Esophageal Epithelium of Achalasia Patients. Turkish Journal of Gastroenterology, 37(2), 170–178. https://doi.org/10.5152/tjg.2025.25031
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