TY - JOUR
T1 - Intestinal barrier dysfunction in human necrotizing enterocolitis
AU - Moore, Sarah A.
AU - Nighot, Prashant
AU - Reyes, Cynthia
AU - Rawat, Manmeet
AU - McKee, Jason
AU - Lemon, David
AU - Hanson, Joshua
AU - Ma, Thomas Y.
N1 - Publisher Copyright:
© 2016
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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 ± 1.65 Ω/cm2 in NEC specimens, 23.36 ± 1.48 Ω/cm2 at resection margin, and 46.48 ± 5.65 Ω/cm2 in controls. Average flux of permeability marker mannitol was 0.23 ± 0.06 μMol/cm2 per h in NEC, 0.04 ± 0.01 μMol/cm2 per h at resection margin, and 0.017 ± 0.004 μMol/cm2 per 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. Conclusion 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. Level of evidence Level 2.
AB - 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 ± 1.65 Ω/cm2 in NEC specimens, 23.36 ± 1.48 Ω/cm2 at resection margin, and 46.48 ± 5.65 Ω/cm2 in controls. Average flux of permeability marker mannitol was 0.23 ± 0.06 μMol/cm2 per h in NEC, 0.04 ± 0.01 μMol/cm2 per h at resection margin, and 0.017 ± 0.004 μMol/cm2 per 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. Conclusion 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. Level of evidence Level 2.
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U2 - 10.1016/j.jpedsurg.2016.09.011
DO - 10.1016/j.jpedsurg.2016.09.011
M3 - Article
C2 - 27720222
AN - SCOPUS:85001129934
SN - 0022-3468
VL - 51
SP - 1907
EP - 1913
JO - Journal of pediatric surgery
JF - Journal of pediatric surgery
IS - 12
ER -