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Identification of a new WASP and FKBP-like (WAFL) protein in inflammatory bowel disease: a potential marker gene for ulcerative colitis

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Abstract

Background and aims

Inflammatory bowel disease (IBD) is a complex inflammatory disease of the gastrointestinal tract with unknown cause that lacks molecular markers for diagnosis. Crohn’s disease (CD) and ulcerative colitis (UC) are the two major forms of IBD. The aim of this study was to investigate gene expression patterns in UC and characterize newly identified marker genes potentially linked to disease pathogenesis of UC.

Materials and methods

Biopsies were taken from eight UC patients, from inflamed and non-inflamed parts of the colon. Gene expression was investigated by subtractive suppression hybridization (SSH), and further study of a selected gene was performed by Northern blot, immunohistochemistry, immunocytochemistry, and in vitro monocyte differentiation.

Results

Three hundred thirty-one differentially expressed genes were found and classified into functional groups. In this paper, we report one gene with unknown function to be differentially expressed in UC but not Crohn’s disease by real-time reverse transcriptase polymerase chain reaction. Due to its predicted protein architecture, we call this gene Wiskott–Aldrich syndrome protein and FKBP-like (WAFL). Initial pilot experiments suggest WAFL to participate in innate immune functions.

Conclusion

The SSH result supports the current view of UC to be a chronic inflammatory disorder with aberrant expression of epithelial barrier proteins, cell fate-related factors, and disturbed metabolism. The new gene, WAFL, reported in this study, appears to be conditionally regulated in myeloid cells. This indicates that WAFL may be connected to innate immune-host responses. As such, it represents an interesting, hitherto unknown player in IBD where there is a need for further elucidation on the molecular and cellular level.

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Acknowledgment

This project was supported by grants from Swedish Research Council and Swedish Foundation for Strategic Research, and VINNOVA Sweden. Marco Daperno received a grant from Fondazione IBD Onlus, Italy, funded by Compagnia di San Paolo The authors would like to thank the Human Proteome Resource for the immunohistological data, Francesca Bresso for coordinating the sampling of the Italian biopsies, and Velmurugesan Arulampalam and Gediminas Grecius for critically reading the manuscript. As a potential conflict of interest, Sven Pettersson and Robert Löfberg are shareholders in InDex Pharmaceuticals AB.

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Authors and Affiliations

  1. Strategic Research Center IRIS, Karolinska Institute, Stockholm, Sweden

    Ing-Marie Viklund, Mauro D’Amato & Sven Pettersson

  2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Nobels väg 16, 171 77, Stockholm, Sweden

    Ing-Marie Viklund, Mauro D’Amato & Sven Pettersson

  3. InDex Pharmaceuticals AB, Stockholm, Sweden

    Nikolai V. Kuznetsov, Oliver von Stein & Petra von Stein

  4. IBD Unit, HMQ Sophia Hospital, Stockholm, Sweden

    Robert Löfberg

  5. Department of Medicine, Karolinska Institute, Stockholm, Sweden

    Robert Löfberg

  6. Gastroenterology Division, A.O. Ordine Mauriziano, Turin, Italy

    Marco Daperno & Raffaello Sostegni

  7. Division of Gastroenterology, University of Torino, Turin, Italy

    Marco Astegiano & Mario Rizzetto

  8. Genome Institute of Singapore, Singapore, Singapore

    Sven Pettersson

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  1. Ing-Marie Viklund
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  8. Oliver von Stein
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  9. Mauro D’Amato
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Corresponding author

Correspondence to Sven Pettersson.

Additional information

Petra von Stein and Sven Pettersson contributed equally to this work

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Viklund, IM., Kuznetsov, N.V., Löfberg, R. et al. Identification of a new WASP and FKBP-like (WAFL) protein in inflammatory bowel disease: a potential marker gene for ulcerative colitis. Int J Colorectal Dis 23, 921–930 (2008). https://doi.org/10.1007/s00384-008-0527-8

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