Activation of REG family proteins in colitis

Abstract

Aims. To do a genome-wide gene expression study of active and inactive ulcerative colitis and Crohn's disease (inflammatory bowel disease – IBD) and examine the most differentially expressed genes. As the study showed an extreme upregulation of all regenerating islet-derived genes (REG proteins) in active IBD, we further studied the expression of REGs on protein level in active and inactive IBD, as well as in non-IBD (pseudomembranous) colitis. Methods. Microarray analysis was done on a total of 100 pinch biopsy samples from healthy controls and patients with Crohn's disease or ulcerative colitis. Tissue samples from IBD and pseudomembranous colitis were examined with routine histology and immunohistochemical analysis for REGIα, REGIV, DEFA6, and serotonin. Results. REG mRNAs were up to 83 times overexpressed in diseased mucosa compared with mucosa from healthy individuals. REGIα and REGIV were overexpressed at immunohistochemistry and located to different mucosal cell types. REGIα was expressed in basal half of crypts, REGIV in mid and outer parts of crypts and in surface epithelium and seems to be stored in, and secreted from, goblets. Pseudomembranous colitis samples showed similar staining patterns, and some IBD samples stained REG positive without inflammation on routine histology. Conclusions. All REG family mRNAs are upregulated in IBD. REGIα and REGIV have different cellular localization, possibly reflecting different biological functions. REG protein expression also in pseudomembranous colitis shows that REG family proteins are regulated in inflammatory injury and repair, not specifically for IBD as previously thought.

Key Words::

• Inflammatory bowel diseases
• REGIA protein human
• REGIV protein human

Acknowledgements

Atle vB Granlund is the recipient of a PhD grant from the Norwegian University of Science and Technology (NTNU) and Ann Elisabeth Østvik of a PhD grant from The Liaison Committee between the Central Norway Regional Health Authority (RHA) and NTNU. This work was also supported by a research grant from The Liaison Committee between St. Olav's University Hospital and the Faculty of Medicine, NTNU. Bjørn Munkvold, Kari Slørdahl and Britt Schulze provided excellent technical assistance. The microarray work was carried out with the support from the National Technology Microarray Platform (Norwegian Microarray Consortium) funded by the Functional Genomics Programme (FUGE) of the Norwegian Research Council. This work was supported in part by a research grant from The Liaison Committee between St. Olav's University Hospital and the Faculty of Medicine, NTNU.

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