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Published in: International Journal of Colorectal Disease 5/2004

01-09-2004 | Original Article

Expression of apoptosis-related proteins in rat with induced colitis

Authors: Giuseppe D’Argenio, Maria Grazia Farrace, Vittorio Cosenza, Francesca De Ritis, Nicola Della Valle, Francesco Manguso, Mauro Piacentini

Published in: International Journal of Colorectal Disease | Issue 5/2004

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Abstract

Background and aims

Inflammatory bowel diseases (IBD) evoke a damage-repair process accompanied by the activation of apoptotic genes. Data on transglutaminase (TG) expression in apoptotic cells in inflamed colonic epithelium has not been reported, although TG cross-links proteins within typical apoptotic bodies in various cell lines. In an experimental model of colitis we investigated the expression of different markers of apoptosis related to the degree and development of colonic inflammation.

Methods

Two studies were performed: (a) Colitis was induced by the administration of 2,4,6-trinitrobenzen sulfonic acid (TNBS) at a dose of 10 or 20 mg per rat in 50% ethanol, and the rats were killed 1 week later; (b) Colitis was induced by 20 mg TNBS and the rats were killed 3 days, 1, 2, and 4 weeks thereafter. The colon of rats was macroscopically assessed, and biopsies were histologically assessed and immunoprobed for FasL, FasR, p53 and tTG. Cell death was detected by TUNEL, and TG activity was assayed on colon homogenates.

Results

Study A: According to enhanced TUNEL positivity, FasR/FasL and p53 expression increased depending on the severity of the colitis. Study B showed increased p53 expression at day 3 while FasR/FasL coexpression peaked at 1 week. In both studies tTG was mainly expressed in the extracellular matrix of damaged tissue and in the submucosa.

Conclusions

Our findings suggest that expression of apoptosis markers is related to the degree of colitis and show that apoptosis is sustained by both p53 and FasR/FasL pathways, depending on the phase of colitis development. Moreover, the lack of TG staining in typical apoptotic bodies may account for a perturbation of the cross-linked apoptotic envelope that may be an important determinant in the development of immune response in ulcerative colitis.
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Metadata
Title
Expression of apoptosis-related proteins in rat with induced colitis
Authors
Giuseppe D’Argenio
Maria Grazia Farrace
Vittorio Cosenza
Francesca De Ritis
Nicola Della Valle
Francesco Manguso
Mauro Piacentini
Publication date
01-09-2004
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 5/2004
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-004-0585-5

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