High-dose erythropoietin inhibits apoptosis and stimulates proliferation in neonatal rat intestine.
BACKGROUND
Erythropoietin (Epo) receptors are widely expressed in the small bowel of neonatal rats and evidence suggests Epo has important trophic effects in developing bowel.


OBJECTIVE
To compliment in vitro data, we directly examine in vivo the hypotheses that systemic Epo treatment can promote cell division and enterocyte migration, and arrest apoptosis in the ileum of neonatal rats.


METHODS
Epo (5000 U/kg s.c.) or vehicle treatments were given to one week old Sprague-Dawley rats (n = 86) along with timed injections of the thymidine analog 5-bromo-2-deoxyuridine (BrdU, 50mg/kg s.c.) to label DNA synthesis and track newly proliferating cells. To characterize the time course of effects, animals were killed at scheduled times from 30 min to 24 h after treatment. BrdU-containing cells were immunostained and counted in intestinal crypts, villi, and muscle wall of ileum. Effects of Epo on apoptosis were analyzed by TUNEL staining. Calibrated measurements were made to determine the density or relative proportion of BrdU- and TUNEL-positive cells.


RESULTS
Systemic high-dose Epo promoted cell division in intestinal smooth muscle and enterocytes, stimulated migration of intestinal epithelial cells, and arrested apoptosis of enterocytes at the villous tips.


CONCLUSIONS
These data provide in vivo evidence that Epo functions trophically in developing intestine tissues.
McPherson
Ronald J
RJ
University of Washington, Seattle, WA 98195, USA.
Juul
Sandra E
SE
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D020895:Enterocytes / Q000166:cytology* / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007422:Intestines / Q000166:cytology* / Q000187:drug effects; D007700:Kinetics; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004921:Erythropoietin; D001973:Bromodeoxyuridine