RGD Reference Report - P-glycoprotein induction by breast milk attenuates intestinal inflammation in experimental necrotizing enterocolitis. - Rat Genome Database

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P-glycoprotein induction by breast milk attenuates intestinal inflammation in experimental necrotizing enterocolitis.

Authors: Guner, YS  Franklin, AL  Chokshi, NK  Castle, SL  Pontarelli, E  Wang, J  Wang, L  Prasadarao, NV  Upperman, JS  Grishin, AV  Ford, HR 
Citation: Guner YS, etal., Lab Invest. 2011 Nov;91(11):1668-79. doi: 10.1038/labinvest.2011.113. Epub 2011 Jul 25.
RGD ID: 8657143
Pubmed: PMID:21788941   (View Abstract at PubMed)
PMCID: PMC3909679   (View Article at PubMed Central)
DOI: DOI:10.1038/labinvest.2011.113   (Journal Full-text)

P-glycoprotein (Pgp), a product of the multi-drug resistance gene MDR1a, is a broad specificity efflux ATP cassette transmembrane transporter that is predominantly expressed in epithelial tissues. Because mdr1a(-/-) mice tend to develop spontaneous colitis in bacteria-dependent manner, Pgp is believed to have a role in protection of the intestinal epithelium from luminal bacteria. Here we demonstrate that levels of Pgp in the small intestine of newborn rodents dramatically increase during breastfeeding, but not during formula feeding (FF). In rats and mice, levels of intestinal Pgp peak on days 3-7 and 1-5 of breastfeeding, respectively. The mdr1a(-/-) neonatal mice subjected to FF, hypoxia, and hypothermia have significantly higher incidence and pathology, as well as significantly earlier onset of necrotizing enterocolitis (NEC) than congenic wild type mice. Breast-fed mdr1a(-/-) neonatal mice are also more susceptible to intestinal damage caused by the opportunistic pathogen Cronobacter sakazakii that has been associated with hospital outbreaks of NEC. Breast milk, but not formula, induces Pgp expression in enterocyte cell lines in a dose- and time-dependent manner. High levels of ectopically expressed Pgp protect epithelial cells in vitro from apoptosis induced by C. sakazakii. Taken together, these results show that breast milk-induced expression of Pgp may have a role in the protection of the neonatal intestinal epithelium from injury associated with nascent bacterial colonization.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ABCB1Humanperinatal necrotizing enterocolitis susceptibilityISOAbcb1a (Mus musculus) RGD 
Abcb1aRatperinatal necrotizing enterocolitis susceptibilityISOAbcb1a (Mus musculus) RGD 
Abcb1aMouseperinatal necrotizing enterocolitis susceptibilityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb1a  (ATP binding cassette subfamily B member 1A)

Genes (Mus musculus)
Abcb1a  (ATP-binding cassette, sub-family B member 1A)

Genes (Homo sapiens)
ABCB1  (ATP binding cassette subfamily B member 1)


Additional Information