Macrophage-derived IGF-1 protects the neonatal intestine against necrotizing enterocolitis by promoting microvascular development

Xiaocai Yan, Elizabeth Managlia, You Yang Zhao, Xiao Di Tan, Isabelle G. De Plaen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Necrotizing enterocolitis (NEC) is a deadly bowel necrotic disease of premature infants. Low levels of plasma IGF-1 predispose premature infants to NEC. While increasing evidence suggests that defective perinatal intestinal microvascular development plays a role in NEC, the involved mechanism remains incompletely understood. We report here that serum and intestinal IGF-1 are developmentally regulated during the perinatal period in mice and decrease during experimental NEC. Neonatal intestinal macrophages produce IGF-1 and promote endothelial cell sprouting in vitro via IGF-1 signaling. In vivo, in the neonatal intestine, macrophage-derived IGF-1 promotes VEGF expression and endothelial cell proliferation and protects against experimental NEC. Exogenous IGF-1 preserves intestinal microvascular density and protects against experimental NEC. In human NEC tissues, villous endothelial cell proliferation and IGF-1- producing macrophages are decreased compared to controls. Together, our results suggest that defective IGF-1-production by neonatal macrophages impairs neonatal intestinal microvascular development and predisposes the intestine to necrotizing enterocolitis.

Original languageEnglish (US)
Article number320
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology
  • Medicine (miscellaneous)

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