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Article

Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis

by
Sabrina Ceccariglia
1,
Diego Sibilia
1,2,
Alice Scattolini
1,
Valentina Saccone
1,2,
Ornella Parolini
1,3,
Alessandro Armuzzi
4,
Alfredo Papa
5,6,
Antonio Gasbarrini
5,6 and
Fabrizio Pizzolante
5,*
1
Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
2
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
3
Fondazione IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy
4
IBD Center IRCSS, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
5
CEMAD (Digestive Disease Center), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
6
Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(13), 5810; https://doi.org/10.3390/ijms27135810
Submission received: 11 May 2026 / Revised: 24 June 2026 / Accepted: 25 June 2026 / Published: 27 June 2026
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Abstract

Endothelial VEGFR-2 plays a central role in vascular remodeling during intestinal inflammation, yet its activation during the early stages of colitis remains poorly characterized. Because Akt is a major downstream effector of VEGFR-2 signaling and a key mediator of endothelial responses, we investigated whether VEGFR-2 phosphorylation and Akt activation occur during the early phase of TNBS-induced colitis before the development of extensive mucosal injury. Acute colitis was induced in adult female Wistar rats by intracolonic administration of TNBS. Colonic tissues were collected on days 2, 4, and 6 after induction. Histological analyses and macrophage (CD68+ cells) infiltration were performed to characterize disease progression. VEGFR-2 expression and phosphorylation at Tyr1175 were evaluated on day 4 by Western blot, immunoprecipitation, and immunofluorescence. Akt activation was also assessed. TNBS-induced colitis is characterized by histological injury and increased CD68+ macrophage infiltration on day 4, with severe tissue damage observed on day 6. On day 4, colitis is associated with increased endothelial VEGFR-2 expression, enhanced VEGFR-2 phosphorylation at Tyr1175, and Akt activation. Early TNBS-induced colitis is associated with endothelial VEGFR-2 phosphorylation and Akt activation before the onset of extensive mucosal destruction on day 6. These findings support activation of the VEGFR-2/Akt signaling axis as an early vascular response during intestinal inflammation and suggest its potential contribution to disease progression.
Keywords: TNBS colitis; VEGF-A expression; VEGFR-2 activation; endothelial response; inflammatory bowel disease TNBS colitis; VEGF-A expression; VEGFR-2 activation; endothelial response; inflammatory bowel disease
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MDPI and ACS Style

Ceccariglia, S.; Sibilia, D.; Scattolini, A.; Saccone, V.; Parolini, O.; Armuzzi, A.; Papa, A.; Gasbarrini, A.; Pizzolante, F. Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis. Int. J. Mol. Sci. 2026, 27, 5810. https://doi.org/10.3390/ijms27135810

AMA Style

Ceccariglia S, Sibilia D, Scattolini A, Saccone V, Parolini O, Armuzzi A, Papa A, Gasbarrini A, Pizzolante F. Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis. International Journal of Molecular Sciences. 2026; 27(13):5810. https://doi.org/10.3390/ijms27135810

Chicago/Turabian Style

Ceccariglia, Sabrina, Diego Sibilia, Alice Scattolini, Valentina Saccone, Ornella Parolini, Alessandro Armuzzi, Alfredo Papa, Antonio Gasbarrini, and Fabrizio Pizzolante. 2026. "Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis" International Journal of Molecular Sciences 27, no. 13: 5810. https://doi.org/10.3390/ijms27135810

APA Style

Ceccariglia, S., Sibilia, D., Scattolini, A., Saccone, V., Parolini, O., Armuzzi, A., Papa, A., Gasbarrini, A., & Pizzolante, F. (2026). Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis. International Journal of Molecular Sciences, 27(13), 5810. https://doi.org/10.3390/ijms27135810

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