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https://hdl.handle.net/2440/79733
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Type: | Journal article |
Title: | Notch signaling promotes intestinal crypt fission in the infant rat |
Author: | Cummins, A. Woenig, J. Donato, R. Proctor, S. Howarth, G. Grover, P. |
Citation: | Digestive Diseases and Sciences, 2013; 58(3):678-685 |
Publisher: | Kluwer Academic/Plenum Publ |
Issue Date: | 2013 |
ISSN: | 0163-2116 1573-2568 |
Statement of Responsibility: | Adrian G. Cummins, Joshua A. Woenig, Rino P. Donato, Simon J. Proctor, Gordon S. Howarth, Phulwinder K. Grover |
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. |
Keywords: | Apoptosis Crypt fission Intestinal growth Notch signaling |
Rights: | © Springer Science+Business Media New York 2012 |
DOI: | 10.1007/s10620-012-2422-y |
Published version: | http://dx.doi.org/10.1007/s10620-012-2422-y |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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