The satiety factor apolipoprotein A-IV modulates intestinal epithelial permeability through its interaction with alpha-catenin: implications for inflammatory bowel diseases

Horm Metab Res. 2007 Aug;39(8):601-11. doi: 10.1055/s-2007-984466.

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, alpha1-antichymotrypsin, cyclin C, and the cytosolic adaptor alpha-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 alpha-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 alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins A / genetics
  • Apolipoproteins A / metabolism*
  • Apolipoproteins A / physiology*
  • Caco-2 Cells
  • Cell Membrane Permeability / genetics*
  • Gene Expression Profiling
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HT29 Cells
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • Intercellular Junctions / metabolism
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Satiation / physiology
  • Transfection
  • alpha Catenin / metabolism*

Substances

  • Apolipoproteins A
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • alpha Catenin
  • apolipoprotein A-IV
  • Green Fluorescent Proteins