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

Journal

International Journal of Colorectal Disease

Publisher

Springer Berlin / Heidelberg

ISSN

0179-1958 (Print) 1432-1262 (Online)

Category

Original Article

DOI

10.1007/s00-8

Ing-Marie Viklund1, 2, Nikolai V. Kuznetsov3, Löfberg4, 5, Marco Daperno6, Raffaello Sostegni6, Marco Astegiano7, Rizzetto7, Oliver von Stein3, Mauro D’Amato1, 2, Petra von Stein3 and Sven Pettersson1, 2, 8

(1)

Strategic Research Center IRIS, Karolinska Institute, Stockholm, Sweden

(2)

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

(3)

InDex Pharmaceuticals AB, Stockholm, Sweden

(4)

IBD Unit, HMQ Sophia Hospital, Stockholm, Sweden

(5)

Department of Medicine, Karolinska Institute, Stockholm, Sweden

(6)

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

(7)

Division of Gastroenterology, University of Torino, Turin, Italy

(8)

Genome Institute of Singapore, Singapore, Singapore

Accepted: 19 June 2008 Published online: 25 July 2008

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.

Electronic supplementary material The online version of this article (doi:10.1007/s00-8) contains supplementary material, which is available to authorized users.

Keywords Inflammatory bowel disease - Ulcerative colitis - Subtractive suppression hybridization - WASP and FKBP-like (WAFL) - KIAA0674

Petra von Stein and Sven Pettersson contributed equally to this work