Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins.
BACKGROUND
Necrotizing enterocolitis (NEC) is a devastating condition affecting premature infants and leads to high mortality and chronic morbidity. Severe form of NEC is associated with acute renal failure, fluid imbalance, hyponatremia, and acidosis. We investigated the effect of NEC on tight junction (TJ) proteins in kidneys using a NEC mouse model to investigate the basis for the observed renal dysfunction.


METHODS
NEC was induced in C57BL/6 mice by formula feeding and subjecting them to periods of hypoxia and cold stress. NEC was confirmed by gross and histological examination. We studied various markers of inflammation in kidneys and investigated changes in expression of several TJ proteins and AQP2 using immunofluorecent staining and western blotting.


RESULTS
We found markedly increased expression of NFκB, TGFβ, and ERK1/2 along with claudin-1, -2, -3, -4, -8, and AQP-2 in NEC kidneys. The membrane localization of claudin-2 was altered in the NEC kidneys and its immunostaining signal at TJ was disrupted.


CONCLUSIONS
NEC led to a severe inflammatory response not only in the gut but also in the kidneys. NEC increased expression of several TJ proteins and caused disruption of claudin-2 in renal tubules. These observed changes can help explain some of the clinical findings observed in NEC.
Department of Pediatrics, Brody School of Medicine, East Carolina University, Greenville, North Carolina.
Parvesh M
PM
Garg
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina.
Rodney
R
Tatum
Department of Pediatrics, Brody School of Medicine, East Carolina University, Greenville, North Carolina.
Srikanth
S
Ravisankar
Department of Pediatrics, Brody School of Medicine, East Carolina University, Greenville, North Carolina.|Department of Pediatrics, MetroHealth Hospital, Case Western Reserve University, Cleveland, Ohio.
Prem S
PS
Shekhawat
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina.
Yan-Hua
YH
Chen
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D003080:Cold Temperature; D058639:Cold-Shock Response; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000150:complications; D041943:Infant Formula; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D057167:Claudins; C113371:Cldn2 protein, mouse; D018836:Inflammation Mediators; D062725:Tight Junction Proteins