Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions

Krishnan MohanKumar, Kopperuncholan Namachivayam, Nithya Sivakumar, Natascha G. Alves, Venkataramana Sidhaye, Jayanta K. Das, Yerin Chung, Jerome W. Breslin, Akhil Maheshwari

Research output: Contribution to journalArticlepeer-review

Abstract

Anemia is a frequent diagnosis in critically ill infants, but the clinical implications of severe anemia in these patients remain unclear. In this study, we examined preweaned mice to investigate the effects of severe anemia during early infancy on gut mucosal permeability. C57BL/6 mice were subjected to timed phlebotomy between postnatal days (P) 2-10 to induce severe anemia (hematocrits 20%-24%), and intestinal permeability was tracked longitudinally between P10 and P20 as intestine-to-plasma translocation of enteral macromolecules and bacterial translocation. Epithelial junctions were evaluated by electron microscopy, polymerase chain reactions, immunohistochemistry, and/or enzyme immunoassays on intestinal tissues, Caco-2 intestinal epithelial-like cells, and colonic organoids. Preweaned mouse pups showed an age-related susceptibility to severe anemia, with increased intestinal permeability to enteral macromolecules (dextran, ovalbumin, β-lactoglobulin) and luminal bacteria. Electron micrographs showed increased paracellular permeability and ultrastructural abnormalities of the adherens junctions. These findings were explained by the loss of E-cadherin in epithelial cells, which was caused by destabilization of the E-cadherin (Cdh1) mRNA because of microRNA let-7e-5p binding to the 3'-untranslated region. Severe anemia resulted in a disproportionate and persistent increase in intestinal permeability in preweaned mice because of the disruption of epithelial adherens junctions. These changes are mediated via microRNA let-7e-mediated depletion of Cdh1 mRNA.

Original languageEnglish (US)
Pages (from-to)G705-G716
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume318
Issue number4
DOIs
StatePublished - 2020

Keywords

  • Barrier
  • Cytoskeleton
  • MicroRNA
  • Translocation
  • Tubulin

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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