Int J Med Sci 2013; 10(10):1259-1270. doi:10.7150/ijms.6358

Research Paper

Flotillin-2 Expression in the Human Gut: from a Cell Model to Human Tissue in Health and Inflammatory Bowel Diseases

Annika Gauss1, Inga Buchholz1, Alexandra Zahn1, Gerd Schmitz2, Wolfgang Stremmel1, Joachim Fuellekrug1, Robert Ehehalt1✉

1. University Hospital Heidelberg, Department of Gastroenterology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany;
2. University Hospital Regensburg, Department of Clinical Chemistry and Laboratory Medicine, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

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Citation:
Gauss A, Buchholz I, Zahn A, Schmitz G, Stremmel W, Fuellekrug J, Ehehalt R. Flotillin-2 Expression in the Human Gut: from a Cell Model to Human Tissue in Health and Inflammatory Bowel Diseases. Int J Med Sci 2013; 10(10):1259-1270. doi:10.7150/ijms.6358. Available from http://www.medsci.org/v10p1259.htm

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Abstract

Background and aims: The etiopathogenesis of inflammatory bowel diseases (IBD) remains largely unexplained. Flotillins (flotillin-1 and flotillin-2) are ubiquitous proteins which have been linked to inflammation and regeneration. We hypothesized that alterations in the expression of flotillin-2 in enterocytes may be related to the pathogenesis of IBD as a classical example of an inflammatory disorder of mostly unknown origin.

Methods: Cell and tissue localization of flotillin-2 (and -1) were investigated by immunofluorescent staining in 1. polarized and unpolarized CaCo-2w cells as a model of human enterocytes (native and after TNFα stimulation) and 2. intestinal biopsies from controls, patients with ulcerative colitis (UC) and patients with Crohn's disease (CD). For quantification of flotillin-2, we analyzed its expression in ileal and colonic biopsies from controls, UC patients and CD patients using real-time RT-PCR, Western blot and indirect immunofluorescence.

Results: In polarized CaCo-2w cells and human enterocytes in biopsies, flotillins were localized at the basolateral membrane and on subapical vesicles, but not in the apical membrane. Flotillin-2 expression did not differ between UC patients, CD patients and controls. However, it was significantly higher in colonic biopsies compared to ileal biopsies in all groups.

Conclusions: By virtue of its abundant expression in enterocytes, flotillin-2 must have an essential function in intestinal physiology, especially in the colon. Yet our data could not link flotillin-2 to the pathogenesis of IBD.

Keywords: Inflammatory bowel disease (IBD), Ulcerative colitis, Crohn's disease, Lipid raft, Flotillin-1, Flotillin-2.