title: The satiety factor apolipoprotein A-IV modulates intestinal epithelial permeability through its interaction with alpha-catenin: implications for inflammatory bowel diseases.
abstract: BACKGROUND
  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.
authors: Institute for Clinical Chemistry and Laboratory Medicine, University Clinic of Regensburg, Regensburg, and Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany. evelyn.orso@klinik.uni-regensburg.de
authors: E
authors: E
authors: Orsó
authors: C
authors: C
authors: Moehle
authors: A
authors: A
authors: Boettcher
authors: K
authors: K
authors: Szakszon
authors: T
authors: T
authors: Werner
authors: T
authors: T
authors: Langmann
authors: G
authors: G
authors: Liebisch
authors: C
authors: C
authors: Buechler
authors: M
authors: M
authors: Ritter
authors: F
authors: F
authors: Kronenberg
authors: H
authors: H
authors: Dieplinger
authors: S R
authors: SR
authors: Bornstein
authors: W
authors: W
authors: Stremmel
authors: G
authors: G
authors: Schmitz
mesh_terms: D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000235:genetics*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007365:Intercellular Junctions / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012527:Satiation / Q000502:physiology; D014162:Transfection; D051178:alpha Catenin / Q000378:metabolism*
chemical_list: D001054:Apolipoproteins A; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin; C022205:apolipoprotein A-IV; D049452:Green Fluorescent Proteins