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 language | English (US) |
|---|---|
| Article number | 320 |
| Journal | Communications Biology |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2022 |
Funding
We would like to thank Marissa Docter for her technical assistance in conducting the NEC model. This work was funded by the National Institute of Health Grants R01 DK116568 (I.G. De Plaen) and R01 GM117628, DK129960 (X. Tan), by Takeda Pharmaceuticals (I.G. De Plaen) and the Stanley Manne Children’s Research Institute of the Ann & Robert H. Lurie Children’s Hospital of Chicago (I.G. De Plaen).
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General Biochemistry, Genetics and Molecular Biology
- Medicine (miscellaneous)
