title: Intestinal barrier dysfunction in human necrotizing enterocolitis.
abstract: BACKGROUND
  Intestinal barrier dysfunction has been implicated in necrotizing enterocolitis (NEC), but has not been directly measured in human NEC.
  
  
  METHODS
  Small intestines removed during surgery were immediately mounted in an Ussing chamber. mRNA expression of tight junction (TJ) proteins was measured with RT-PCR.
  
  
  RESULTS
  Fifteen infants were included, 5 with NEC and 10 with other diagnoses. Average transepithelial resistance (TER) was 11.61±1.65Ω/cm2in NEC specimens, 23.36±1.48Ω/cm2at resection margin, and 46.48±5.65Ω/cm2in controls. Average flux of permeability marker mannitol was 0.23±0.06μMol/cm2per h in NEC, 0.04±0.01 μMol/cm2per h at resection margin, and 0.017±0.004 μMol/cm2per h in control tissue (p<0.05). RT-PCR analysis showed marked decrease in mRNA expression of a TJ protein occludin in NEC affected tissue (p<0.03 vs. control). Additionally, mRNA expression of myosin light chain kinase (MLCK), an important regulator of TJ permeability, was increased in NEC specimens.
  
  
  CONCLUSIONS
  These studies show for the first time that NEC intestinal tissue have increased intestinal permeability, even at grossly healthy-appearing resection areas. The increase in intestinal permeability in NEC appeared to be related in part to a decrease in occludin and an increase in MLCK expression.
  
  
  METHODS
  Level 2.
authors.affiliation: Department of Surgery, University of New Mexico, MSC10 5610 1 UNM, Albuquerque, NM 87131.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Moore
authors.affiliation: Department of Internal Medicine, University of New Mexico, MSC10-5550, Albuquerque, NM 87131.
authors.forename: Prashant
authors.initials: P
authors.lastname: Nighot
authors.affiliation: Department of Surgery, University of New Mexico, MSC10 5610 1 UNM, Albuquerque, NM 87131. Electronic address: CYReyes@salud.unm.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Reyes
authors.affiliation: Department of Internal Medicine, University of New Mexico, MSC10-5550, Albuquerque, NM 87131.
authors.forename: Manmeet
authors.initials: M
authors.lastname: Rawat
authors.affiliation: Department of Surgery, University of New Mexico, MSC10 5610 1 UNM, Albuquerque, NM 87131.
authors.forename: Jason
authors.initials: J
authors.lastname: McKee
authors.affiliation: Department of Surgery, University of New Mexico, MSC10 5610 1 UNM, Albuquerque, NM 87131.
authors.forename: David
authors.initials: D
authors.lastname: Lemon
authors.affiliation: Department of Pathology, University of New Mexico, MSC08-4640, Albuquerque, NM 87131.
authors.forename: Joshua
authors.initials: J
authors.lastname: Hanson
authors.affiliation: Department of Internal Medicine, University of New Mexico, MSC10-5550, Albuquerque, NM 87131. Electronic address: TMa@salud.unm.edu.
authors.forename: Thomas Y
authors.initials: TY
authors.lastname: Ma
mesh_terms: D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology*; D007421:Intestine, Small / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000096:biosynthesis; D062793:Occludin / Q000096:biosynthesis; D010539:Permeability; D012333:RNA, Messenger / Q000096:biosynthesis; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D062793:Occludin; D012333:RNA, Messenger; D009219:Myosin-Light-Chain Kinase
keywords: Intestinal barrier function; Necrotizing enterocolitis; Occludin; Tight junction