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Horm Metab Res 2007; 39(8): 601-611
DOI: 10.1055/s-2007-984466
Clinical Human

© Georg Thieme Verlag KG Stuttgart · New York

The Satiety Factor Apolipoprotein A-IV Modulates Intestinal Epithelial Permeability through its Interaction with α-Catenin: Implications for Inflammatory Bowel Diseases

E. Orsó 1 , C. Moehle 1 , A. Boettcher 1 , K. Szakszon 1 , T. Werner 1 , T. Langmann 1 , G. Liebisch 1 , C. Buechler 1 , M. Ritter 1 , F. Kronenberg 2 , H. Dieplinger 2 , S. R. Bornstein 3 , W. Stremmel 4 , G. Schmitz 1
  • 1Institute for Clinical Chemistry and Laboratory Medicine, University Clinic of Regensburg, Regensburg, Germany
  • 2Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
  • 3Medical Clinic III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
  • 4Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
Further Information

Publication History

received 03.03.2007

accepted 29.05.2007

Publication Date:
21 August 2007 (online)

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Abstract

Introduction: Apolipoprotein A-IV (apoA-IV), an intestinally and cerebrally synthesized satiety factor and anti-atherogenic plasma apolipoprotein, was recently identified as an anti-inflammatory protein. In order to elucidate whether intestinal apoA-IV exerts similar repair function as its hepatic homologue apolipoprotein A-V (apoA-V), apoA-IV-interactive proteins were searched and in vitro functional studies were performed with apoA-IV overexpressing cells. ApoA-IV was also analyzed in the intestinal mucosa of patients with inflammatory bowel diseases (IBD), together with other genes involved in epithelial junctional integrity.

Methods: A yeast-two-hybrid screening was used to identify apoA-IV-interactors. ApoA-IV was overexpressed in Caco-2 and HT-29 mucosal cells for colocalization and in vitro epithelial permeability studies. Mucosal biopsies from quiescent regions of colon transversum and terminal ileum were subjected to DNA-microarray analysis and pathway-related data mining.

Results: Four proteins interacting with apoA-IV were identified, including apolipoprotein B-100, α1-antichymotrypsin, cyclin C, and the cytosolic adaptor α-catenin, thus linking apoA-IV to adherens junctions. Overexpression of apoA-IV was paralleled with a differentiated phenotype of intestinal epithelial cells, upregulation of junctional proteins, and decreased paracellular permeability. Colocalization between α-catenin and apoA-IV occurred exclusively in junctional complexes. ApoA-IV was downregulated in quiescent mucosal tissues from patients suffering from IBD. In parallel, only a distinct set of junctional genes was dysregulated in non-inflamed regions of IBD gut.

Conclusions: ApoA-IV may act as a stabilizer of adherens junctions interacting with α-catenin, and is likely involved in the maintenance of junctional integrity. ApoA-IV expression is significantly impaired in IBD mucosa, even in non-inflamed regions.

Key words

Apolipoproteins - catenins - intestinal permeability - junctional integrity - inflammatory bowel disease

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Correspondence

E. OrsóMD, PhD, MSc 

Institute for Clinical Chemistry and Laboratory Medicine

University of Regensburg

Franz-Josef-Strauss-Allee 11

93053 Regensburg

Germany

Phone: +49/941/944 62 37

Fax: +49/941/944 62 02

Email: evelyn.orso@klinik.uni-regensburg.de