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


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.


CONCLUSIONS
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.
Viklund
Ing-Marie
IM
Strategic Research Center IRIS, Karolinska Institute, Stockholm, Sweden.
Kuznetsov
Nikolai V
NV
Löfberg
Robert
R
Daperno
Marco
M
Sostegni
Raffaello
R
Astegiano
Marco
M
Rizzetto
Mario
M
von Stein
Oliver
O
D'Amato
Mauro
M
von Stein
Petra
P
Pettersson
Sven
S
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D015152:Blotting, Northern; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D051316:Wiskott-Aldrich Syndrome Protein; D012313:RNA; D022021:Tacrolimus Binding Proteins