{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:44:53Z","timestamp":1782783893269,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms27135810","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial VEGFR-2 Activation Precedes Severe Mucosal Injury in TNBS-Induced Colitis"],"prefix":"10.3390","volume":"27","author":[{"given":"Sabrina","family":"Ceccariglia","sequence":"first","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Sibilia","sequence":"additional","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9989-8638","authenticated-orcid":false,"given":"Alice","family":"Scattolini","sequence":"additional","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Saccone","sequence":"additional","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-6430","authenticated-orcid":false,"given":"Ornella","family":"Parolini","sequence":"additional","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Armuzzi","sequence":"additional","affiliation":[{"name":"IBD Center IRCSS, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-7298","authenticated-orcid":false,"given":"Alfredo","family":"Papa","sequence":"additional","affiliation":[{"name":"CEMAD (Digestive Disease Center), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-1779","authenticated-orcid":false,"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"CEMAD (Digestive Disease Center), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-8232","authenticated-orcid":false,"given":"Fabrizio","family":"Pizzolante","sequence":"additional","affiliation":[{"name":"CEMAD (Digestive Disease Center), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1053\/j.gastro.2006.03.054","article-title":"Angiogenesis as a Novel Component of Inflammatory Bowel Disease Pathogenesis","volume":"130","author":"Danese","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.2353\/ajpath.2008.070593","article-title":"Multiple pathogenic roles of microvasculature in inflammatory bowel disease: A jack of all trades","volume":"172","author":"Deban","year":"2008","journal-title":"Am. 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