Extensive Histopathological Characterization of Inflamed Bowel in the Dextran Sulfate Sodium Mouse Model with Emphasis on Clinically Relevant Biomarkers and Targets for Drug Development

• Published in: International journal of molecular sciences Vol. 22; no. 4; p. 2028
• Main Authors: Bonfiglio, Rita, Galli, Filippo, Varani, Michela, Scimeca, Manuel, Borri, Filippo, Fazi, Sara, Cicconi, Rosella, Mattei, Maurizio, Campagna, Giuseppe, Schönberger, Tanja, Raymond, Ernest, Wunder, Andreas, Signore, Alberto, Bonanno, Elena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 18.02.2021; MDPI AG
• Subjects: Animals; biomarker discovery; Biomarkers - metabolism; Colitis - pathology; Cytokines - metabolism; Dextran Sulfate; dextran sulfate sodium mouse; Disease Models, Animal; Drug Development; Female; histopathology; inflammatory bowel disease; Inflammatory Bowel Diseases - pathology; Integrins - metabolism; Intestinal Mucosa - pathology; Mice; Mice, Inbred C57BL; preclinical model; Vascular Endothelial Growth Factor Receptor-2 - metabolism; histopathology; dextran sulfate sodium mouse; preclinical model; biomarker discovery; inflammatory bowel disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22042028

This study aims to develop a reliable and reproducible inflammatory bowel disease (IBD) murine model based on a careful spatial-temporal histological characterization. Secondary aims included extensive preclinical studies focused on the in situ expression of clinically relevant biomarkers and targets involved in IBD. C57BL/6 female mice were used to establish the IBD model. Colitis was induced by the oral administration of 2% Dextran Sulfate Sodium (DSS) for 5 days, followed by 2, 4 or 9 days of water. Histological analysis was performed by sectioning the whole colon into rings of 5 mm each. Immunohistochemical analyses were performed for molecular targets of interest for monitoring disease activity, treatment response and predicting outcome. Data reported here allowed us to develop an original scoring method useful as a tool for the histological assessment of preclinical models of DSS-induced IBD. Immunohistochemical data showed a significant increase in TNF-α, α4β7, VEGFRII, GR-1, CD25, CD3 and IL-12p40 expression in DSS mice if compared to controls. No difference was observed for IL-17, IL-23R, IL-36R or F480. Knowledge of the spatial-temporal pattern distribution of the pathological lesions of a well-characterized disease model lays the foundation for the study of the tissue expression of meaningful predictive biomarkers, thereby improving translational success rates of preclinical studies for a personalized management of IBD patients.