P0019Activation of vascular endothelial growth factor receptor 2 in a rat model of ulcerative colitis

Abstract Background Pathological angiogenesis, primarily mediated by vascular endothelial growth factor (VEGF) and its receptor VEGFR-2, plays a key role in the pathogenesis of ulcerative colitis (UC). Previous studies have reported increased VEGF and total VEGFR-2 expression in inflamed intestinal tissues, together with activation of downstream signalling pathways (Erk1/2, Src, Akt) and increased vascular permeability. However, the distribution and functional relevance of phosphorylated, active VEGFR-2 in experimental colitis remain poorly characterised. This study aimed to document the presence and localisation of phosphorylated VEGFR-2 in a murine model of colitis and to explore its potential pathogenic and therapeutic implications. Methods Colitis was induced in mice using dextran sodium sulfate (DSS). The expression of phosphorylated VEGFR-2 at tyrosine residues Tyr1175 and Tyr1214 was analysed in colonic tissues by immunohistochemistry and Western blot. Quantitative and qualitative assessments were correlated with histological inflammation scores and vascular changes. Results Phosphorylated VEGFR-2 was markedly increased in colonic endothelial and epithelial cells in DSS-induced colitis compared with controls. The two phosphorylation sites displayed distinct associations: Tyr1175 correlated with enhanced angiogenesis and inflammatory activity, whereas Tyr1214 was more closely related to epithelial responses and mucosal repair Conclusion This study provides the first detailed characterisation of active, phosphorylated VEGFR-2 in an experimental model of colitis. By distinguishing receptor overexpression from functional activation, it advances our understanding of VEGFR-2 signalling in intestinal inflammation. Although not directly assessed here, these findings may also have implications for colitis-associated carcinogenesis and the identification of novel, site-specific therapeutic targets. References: Scaldaferri F, Vetrano S, Sans M, et al. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology. 2009;136(2):585–595.e5. Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G5–G18. Knod JL, Crawford K, Dusing M, Frischer JS. Vascular endothelial growth factor receptor-2 inhibition in experimental murine colitis. J Surg Res. 2014;190(1):47–54. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling — in control of vascular function. Nat Rev Mol Cell Biol. 2006;7(5):359–371. Conflict of interest: Dr. Pizzolante, Fabrizio: AstraZeneca Giuliani Ceccariglia, Sabrina: No conflict of interest Sibilia, Diego: No conflict of interest Scattolini, Alice: No conflict of interest Saccone, Valentina: No conflict of interest Parolini, Ornella: No conflict of interest Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Papa, Alfredo: No conflict of interest Gasbarrini, Antonio: No conflict of interest