Dithizone-induced Paneth cell disruption significantly decreases intestinal perfusion in the murine small intestine

Jennifer N. Berger, Huyiu Gong, Misty Good, Steven J. McElroy

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose: Necrotizing enterocolitis is associated with decreased intestinal perfusion and ischemia. Paneth cells, specialized epithelial cells, have been shown to regulate the intestinal vasculature and disruption of these cells has been associated with NEC. We hypothesized that Paneth cell disruption in immature mice intestine would decrease the perfusion of the intestinal microvasculature. Methods: Paneth cells were disrupted in P14–16 mice using chemical (dithizone) and transgenic (diphtheria toxin) methodology. Six hours after Paneth cell disruption, Dylight 488 was injected directly into the left ventricle and allowed to perfuse for 5 minutes prior to intestinal harvesting. Tissue samples were evaluated with confocal fluorescence microscopy to quantify intestinal perfusion and samples were quantified by real time RT-PCR for gene expression. Results: Dithizone treatment significantly decreased intestinal perfusion compared to controls (p < 0.01). However, diphtheria toxin treatment demonstrated no significant difference in perfusion (p > 0.21). Intestines from all treatment groups had similar PECAM staining, but intestines treated with dithizone had significantly decreased nNOS and iNOS gene expression compared to controls (p < 0.007). Conclusions: Paneth cell disruption significantly decreases the perfusion of the small intestinal microvasculature in a dithizone-specific manner. Dithizone has no effect on the amount of microvasculature, but does impact genes critical to nitric oxide signaling likely contributing to mesenteric vasoconstriction.

Original languageEnglish
Pages (from-to)2402-2407
Number of pages6
JournalJournal of Pediatric Surgery
Volume54
Issue number11
DOIs
StatePublished - Nov 2019

Keywords

  • Animal model
  • Intestinal microvasculature
  • Necrotizing enterocolitis
  • Nitric oxide

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