title: TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an upregulation of intestinal matrix metalloproteinases (MMPs) activity that may play key roles on the higher permeability of the intestinal barrier, typical to NEC. Recently, TIMP-1, a natural inhibitor of MMP's, was found to be over expressed in preterm human breast milk (HBM). Previous studies have shown that infants fed with HBM have a significant reduction in the incidence of NEC. The aim of the present study was to investigate the possible role that TIMP-1 may play on the maintenance of tight junctions and therefore the gut barrier integrity.
  
  
  METHODS
  Timp-1-treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity.
  
  
  RESULTS
  TIMP-1 inhibited MMP-2 activity, which induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosis.
  
  
  CONCLUSIONS
  One of the putative mechanisms associated with HBM protection against NEC is mediated by TIMP-1, which downregulates MMP-2 activity, inhibits the degradation of occluding, and preserves tight junctions and gut barrier integrity.
authors: School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors: Amir
authors: A
authors: Bein
authors: 1] Department of Pediatrics and Neonatology, Tel Aviv Medical Center, Tel Aviv, Israel [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Ronit
authors: R
authors: Lubetzky
authors: 1] Department of Pediatrics and Neonatology, Tel Aviv Medical Center, Tel Aviv, Israel [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Dror
authors: D
authors: Mandel
authors: School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors: Betty
authors: B
authors: Schwartz
mesh_terms: D018938:Caco-2 Cells; D020345:Enterocolitis, Necrotizing / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008895:Milk, Human / Q000378:metabolism; D062793:Occludin / Q000378:metabolism*; D010539:Permeability; D011994:Recombinant Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: C568985:OCLN protein, human; D062793:Occludin; D011994:Recombinant Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2