Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

The Gut-Ex-vivo System (GEVS) Is a Dynamic and Versatile Tool for the Study of Dnbs-Induced IBDin BALB/c and C57BL/6 Mice

Version 1 : Received: 4 April 2022 / Approved: 6 April 2022 / Online: 6 April 2022 (10:40:35 CEST)

How to cite: Monzani, R.; Gagliardi, M.; Clemente, N.; Saverio, V.; Pańczyszyn, E.; Yissachar, N.; Corazzari, M. The Gut-Ex-vivo System (GEVS) Is a Dynamic and Versatile Tool for the Study of Dnbs-Induced IBDin BALB/c and C57BL/6 Mice. Preprints 2022, 2022040042. https://doi.org/10.20944/preprints202204.0042.v1 Monzani, R.; Gagliardi, M.; Clemente, N.; Saverio, V.; Pańczyszyn, E.; Yissachar, N.; Corazzari, M. The Gut-Ex-vivo System (GEVS) Is a Dynamic and Versatile Tool for the Study of Dnbs-Induced IBDin BALB/c and C57BL/6 Mice. Preprints 2022, 2022040042. https://doi.org/10.20944/preprints202204.0042.v1

Abstract

Background: IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against intestinal, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for disease onset and progression are still elusive, thus requiring intense research effort. In this context, the development of models recapitulating the etiopathology of IBD is critical.Methods: Colon from C57BL/6 or BALB/c mice were cultivated in a gut-ex-vivo system (GEVS), exposed 5h to DNBS 1,5 or 2,5 mg/ml, and the main hallmarkers of IBD were evaluated.Results: Gene expression analysis revealed a DNBS-induced: i) compromised Tight junction organization, responsible for tissue permeability dysregulation; induction of ER stress, and iii) tissue inflammation in colon of C57BL/6 mice. Moreover, the concomitant DNBS-induced apoptosis and ferroptosis pathways was evident in colon from both BALB/c and C57BL/6 mice.Conclusions: Overall, we have provided results demonstrating that GEVS is a consistent, reliable, and cost-effective system for modeling DNBS-induced IBD, useful for studying the onset and progression of human disease at the molecular level, while also reducing animal suffering.

Keywords

IBD; UC; UPR; ex vivo organ; DNBS; Gut-Ex-Vivo System; GEVS; ferroptosis; apoptosis

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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