Abstract
Spontaneous intestinal perforations in extremely premature infants are associated with glucocorticoid-induced thinning of the ileal bowel wall. We have previously demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the submucosa of the newborn mouse ileum but is diminished by glucocorticoid exposure, concomitant with bowel wall thinning. These findings prompted us to hypothesize that IGF-I governs submucosal growth during neonatal gut development and that diminished IGF-I abundance results in submucosal thinning. Heterozygous IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were euthanized at 3 d of life. Additionally, wild type newborn mice received daily dexamethasone (DEX) (1μg/gm/d) or vehicle control on days of life 1 and 2 and were also euthanized at 3 d of life. Their ileums were harvested, fixed and the resulting sections were processed in parallel for IGF-I immunohistochemistry and morphometric measurements of submucosal thickness and bowel diameter. Immunolocalization of IGF-I in each genotype was also compared with that seen in DEX-treated and control mice euthanized at the same time of life. IGF-I heterozygous knockouts had diminished submucosal IGF-I immunolocalization (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over-expressers exceeded that seen within wild type mice. IGF-I genotype and submucosal abundance was positively correlated with ileal submucosal thickness. DEX treatment of newborn mice diminished IGF-I and caused significant thinning of the submucosa compared with controls. Submucosal growth and thickness in the neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone treatment.
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Abbreviations
- DEX:
-
dexamethasone
- OE:
-
over-expressor
- KO:
-
knockout
- WT:
-
wild type
- IGF-1:
-
insulin-like growth factor-1
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The authors thank Sarabeth L. Thomas M.S., for proof reading and helpful discussions.
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Support for this project was provided through grants from the NIH: CHRCDA HD01421 (P.V.G) and NIDDK 1KO8DK/HD61553-01 (P.V.G.).
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Herman, A., Carlisle, E., Paxton, J. et al. Insulin-like Growth Factor-I Governs Submucosal Growth and Thickness in the Newborn Mouse Ileum. Pediatr Res 55, 507–513 (2004). https://doi.org/10.1203/01.PDR.0000110525.30786.50
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DOI: https://doi.org/10.1203/01.PDR.0000110525.30786.50
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