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Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat.
- Source :
-
Apoptosis : an international journal on programmed cell death [Apoptosis] 2008 Nov; Vol. 13 (11), pp. 1344-55. - Publication Year :
- 2008
-
Abstract
- The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.
- Subjects :
- Animals
Caco-2 Cells
Enterocytes metabolism
Enzyme Inhibitors pharmacology
Humans
Male
Proto-Oncogene Proteins c-bcl-2 metabolism
Rats
Rats, Sprague-Dawley
bcl-2-Associated X Protein metabolism
Apoptosis
Enterocytes pathology
ErbB Receptors metabolism
Gene Expression Regulation
Intestinal Mucosa pathology
Methotrexate pharmacology
Transforming Growth Factor alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-675X
- Volume :
- 13
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Publication Type :
- Academic Journal
- Accession number :
- 18803016
- Full Text :
- https://doi.org/10.1007/s10495-008-0258-x