Igf-I accelerates ileal epithelial cell migration in culture and newborn mice and may be a mediator of steroid-induced maturation.
We have previously hypothesized that IGF-I is a mediator of dexamethasone (DEX) effect in the newborn mouse ileum-a model designed to mimic the precocious mucosal maturation associated with spontaneous ileal perforations in extremely premature neonates. We have further investigated this hypothesis using in vivo and in vitro models of accelerated epithelial migration (a transient property, temporally associated with mucosal maturation). These experiments include a steroid-treatment model comparing IGF-I immunolocalization with bromo-deoxyuridine (BrdU)-pulse-labeling, as a means of assessing epithelial cell migration, within the ileum of newborn mice that received either daily intraperitoneal injections of DEX (1 microg/gm) or vehicle. Likewise, a transgenic newborn mouse model was used to compare the effect of IGF-I overexpression upon the clearance of BrdU-pulse-labeled epithelial cells traveling up the villus during the same time period. For our in vitro model, rat ileal epithelial cells (IEC-18) were cultured to confluence in serum-free media then treated with DEX, a stable IGF-I agonist, or nothing before being subjected to linear scarification. Serial photomicrographs of migrating cells were taken over time and the average speed was determined for each treatment condition. Our data demonstrate that IGF-I accelerates ileal epithelial cell migration in every model. However, DEX was only associated with accelerated epithelial cell migration in models where IGF-I (or a synthetic agonist) was highly abundant. In contrast, DEX by itself slowed migration speed in cell culture. These findings suggest that IGF-I may be a mediator of steroid effect during precocious maturation of the ileal mucosa.
Gordon
Phillip V
PV
Department of Pediatrics, Division of Neomatology, University of Virginia Health Sciences, Charlottesville, VA 22908, USA. pvg4n@virginia.edu
Paxton
Jessica B
JB
Herman
Andrew C
AC
Carlisle
Erica M
EM
Fox
Nena S
NS
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D005938:Glucocorticoids / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000166:cytology; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D051381:Rats
D002352:Carrier Proteins; D005938:Glucocorticoids; D008840:Microfilament Proteins; C026615:villin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone