University of Oulu

Nortunen, M., Väkiparta, N., Parkkila, S. et al. Carbonic Anhydrases II, IX, and XII in Reflux Esophagitis. Dig Dis Sci 67, 1761–1772 (2022).

Carbonic anhydrases II, IX, and XII in reflux esophagitis

Saved in:
Author: Nortunen, Minna1,2,3; Väkiparta, Nina1,2,3; Parkkila, Seppo4;
Organizations: 1Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
2Anesthesia and Intensive Care, Research Unit of Surgery, University of Oulu, Oulu, Finland
3Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
4Faculty of Medicine and Health Technology, Tampere University and Fimlab Ltd, Tampere University Hospital, 33520, Tampere, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2022
Publish Date: 2022-08-30


Background: The pathogenesis of gastroesophageal reflux disease (GERD) has not been resolved in detail. Esophageal epithelial cells provide resistance to acidic reflux via several mechanisms, many of which involve buffering acid with bicarbonate and transporting protons. Carbonic anhydrases (CAs) are enzymes that control the acid–base balance by catalyzing the reversible hydration of carbon dioxide to produce bicarbonate and hydrogen ions.

Aims: We aimed to determine the immunohistochemical expression patterns of CAII, CAIX, and CAXII in the normal esophageal squamous epithelium and in patients with GERD.

Methods: We evaluated 82 biopsy samples, including 26 with a histologically normal esophagus, 26 with histologically mild esophagitis, and 30 with severe esophagitis. Expression patterns of CAII, CAIX, and CAXII in the esophageal squamous epithelium were determined by immunohistochemical staining.

Results: Cytoplasmic CAII expression was predominantly detected in the upper luminal part of the squamous epithelium and was significantly (p < 0.01) increased in GERD. Expression of CAIX was essentially membranous. The isozyme was constantly present in the peripapillary cells. In the interpapillary areas, clustered expression was observed to emerge and increase significantly (p < 0.01) in esophagitis. CAXII expression was the most abundant of the isozymes and was mainly membranous. In the normal squamous epithelium, CAXII expression was confined to the basal layer; in severe esophagitis, CAXII expression increased significantly in both basal (p < 0.05) and superficial (p < 0.01) halves of the epithelium.

Conclusions: We demonstrate upregulated expression of CAII, CAIX, and CAXII in GERD. The increase in expression likely contributes to esophageal epithelial resistance to acidic reflux.

see all

Series: Digestive diseases and sciences
ISSN: 0163-2116
ISSN-E: 1573-2568
ISSN-L: 0163-2116
Volume: 67
Issue: 5
Pages: 1761 - 1772
DOI: 10.1007/s10620-021-06985-5
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: Open access funding provided by University of Oulu including Oulu University Hospital. This study was funded by Mary and Georg C. Ehrnroots Foundation (HH) and Thelma Mäkikyrö Foundation (HH).
Copyright information: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit