Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease

Abstract

Background. Claudins, being part of the tight junction protein family, partially determine the integrity and paracellular permeability of the intestinal epithelium. The aim of this study was twofold. First, the authors set out to create an overview of claudin mRNA expression along the proximal-distal axis of the healthy human intestine. Second, the authors aimed to analyze expression levels of claudins in patients with active and inactive inflammatory bowel diseases (IBD) such as Crohn's disease or ulcerative colitis (UC). Methods. mRNA expression levels of claudins were determined in gastrointestinal biopsies from healthy patients as well as patients diagnosed with IBD using SybrGreen real-time PCR. Results. Claudins show distinct expression patterns throughout the gastrointestinal tract. Some claudins show a proximal expression pattern, such as CLDN18 which is solely expressed in the stomach, and CLDN2 and -15 that are predominantly expressed in the proximal parts of the gastrointestinal tract. Other claudins, such as CLDN3, -4, -7 and -8, are predominantly expressed in the distal parts of the gastrointestinal tract or show a ubiquitous expression pattern throughout the entire gastrointestinal tract, which is the case for CLDN12. In addition, we show that changes in claudin expression in IBD are dependent on gastrointestinal location and inflammatory activity. Conclusions. This study provides detailed mRNA expression patterns of various claudins throughout the human gastrointestinal tract. Analysis of expression levels of claudins in patients with CD, active and inactive UC shows that changes in expression are confined to specific intestinal segments and strongly depend on inflammatory activity.

Key Words::

• claudins
• inflammatory bowel disease
• intestine

Acknowledgments

The expert assistance of Mrs Maire Kulmala, RN, is gratefully acknowledged. This study was supported by funding from the Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; the Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland; Competitive Research Funding of Tampere University Hospital; the Academy of Finland; the Sigrid Juselius Foundation; J. Hoenderop was supported by a EURYI award from the European Science Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.