Notch signaling promotes intestinal crypt fission in the infant rat.
Dig Dis Sci
; 58(3): 678-85, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23053894
ABSTRACT
BACKGROUND:
Growth of the small intestine in the infant rat is promoted by crypt fission and later by increased crypt cell proliferation. Notch signaling could promote crypt fission. Hes-1 is a Notch target gene.AIM:
We assessed the effect of Notch signaling on intestinal crypt fission and on growth of the intestine in the infant rat.METHODS:
Hes-1 expression was determined in the small intestine of litters of Hooded Wistar rats aged between 3 and 72 days. Hes-1 RNA expression was measured by quantitative RT-PCR. Four groups of rats (n = 8 or 9) were injected daily, ip, either with vehicle or with the Notch inhibitor DAPT at doses of 3, 10, and 30 mg/kg, from days 9 to 13 of life, and killed on day 14. A microdissection technique was used to measure crypt fission, mitotic count, and apoptotic count. Data were analyzed by ANOVA and by use of Dunnett's F test.RESULTS:
Hes-1 expression and crypt fission peaked on day 14. DAPT reduced Hes-1 immunostaining in proportion to dose. DAPT reduced villous area to 72 % (p < 0.01), 53 % (p < 0.001), and 38 % (p < 0.001) of control values for 3, 10 and 30 mg/kg doses, respectively, and reduced crypt fission to 53 % (p < 0.001) and 38 % (p < 0.001) of control values, respectively, for 10 and 30 mg/kg doses. Crypt mitotic count was not affected by any DAPT dose. DAPT at 10 and 30 mg/kg significantly increased apoptosis in crypts, by 6.5 and 4.8-fold, respectively.CONCLUSIONS:
We conclude that Notch signaling promotes crypt fission and growth of the intestine by maintaining low apoptosis of crypt cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Receptores Notch
/
Intestino Delgado
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article