NDA@SZTAKI

Structural and molecular features of intestinal strictures in rats with Crohn's-like disease

Talapka, Petra

BerkĂł, AnikĂł

Nagy, Lajos

Chandrakumar, Lalitha

Bagyánszki, Mária

Puskás, László Géza

Fekete, Éva

BĂłdi, Nikolett

Beijing Baishideng BioMed Scientific Co.

2016-06-14

R850-854 Experimental medicine / kisérleti orvostudomány

RC658.5 Diabetes / diabetolĂłgia

AIM: To develop a new rat model we wanted to gain a
better understanding of stricture formation in Crohn’s
disease (CD).
METHODS: Chronic colitis was induced locally by the
administration of 2,4,6-trinitrobenzenesulfonic acid
(TNBS). The relapsing inflammation characteristic
to CD was mimicked by repeated TNBS treatments.
Animals were randomly divided into control, once,
twice and three times TNBS-treated groups. Control
animals received an enema of saline. Tissue samples
were taken from the strictured colonic segments and
also adjacent proximally and distally to its 60, 90 or
120 d after the last TNBS or saline administrations.
The frequency and macroscopic extent of the strictures
were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9 (MMP9)
and TIMP1 mRNA and protein expression were determined
by quantitative real-time PCR and western blot
analysis. The quantitative distribution of caspase 9 was
determined by post-embedding immunohistochemistry.
RESULTS: Intestinal strictures first appeared 60 d
after TNBS treatments and the frequency of them
increased up to day 120. From day 90 an intact lamina
epithelialis, reversible thickening of lamina muscularis
mucosae and irreversible thickening of the muscularis
externa were demonstrated in the strictured colonic
segments. Nevertheless the morphological signs of
apoptosis were frequently seen and excess extracellular
matrix deposition was recorded between smooth muscle
cells (SMCs). Enhanced caspase 9 expression on day 90
in the SMCs and on day 120 also in myenteric neurons
indicated the induction of apoptosis. The mRNA
expression profile of TGF-betas after repeated TNBS
doses was characteristic to CD, TGF-beta 2, but not
TGF-beta 3 was up-regulated. Overexpression of MMP9
and down-regulation of TIMP1 were demonstrated. The
progressive increase in the amount of MMP9 protein in
the strictures was also obvious between days 90 and
120 but TIMP1 protein was practically undetectable at
this time.
CONCLUSION: These findings indicate that aligned
structural and molecular changes in the gut wall rather
than neuronal cell death play the primary role in
stricture formation.

magyar

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/41170/1/WJG-22-5154.pdf

Talapka, Petra and Berkó, Anikó and Nagy, Lajos and Chandrakumar, Lalitha and Bagyánszki, Mária and Puskás, László Géza and Fekete, Éva and Bódi, Nikolett (2016) Structural and molecular features of intestinal strictures in rats with Crohn's-like disease. World Journal of Gastroenterology. ISSN 1007-9327 (print), 2219-2840 (online)

http://real.mtak.hu/41170/