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Here, we explored the pathogenesis underlying the intestinal inflammation in COVID\u201019. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS\u2010CoV\u20102 spike protein, we further revealed that VEGF was over\u2010produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS\u2010CoV\u20102 spike promoted VEGF production through activating the Ras\u2010Raf\u2010MEK\u2010ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK\/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID\u201019.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202114844","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T01:13:21Z","timestamp":1648775601000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["SARS\u2010CoV\u20102 spike spurs intestinal inflammation via VEGF production in enterocytes"],"prefix":"10.1038","volume":"14","author":[{"given":"Fa\u2010Min","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010hua","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010zhong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoming","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan\u2010Min","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-8475","authenticated-orcid":false,"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-2700","authenticated-orcid":false,"given":"Fei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5214-0134","authenticated-orcid":false,"given":"Ye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6640-1390","authenticated-orcid":false,"given":"Hong","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-0840","authenticated-orcid":false,"given":"Huanhuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"BFEMMM202114844_CR1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1167\/iovs.07-1129","volume":"50","author":"F Bock","year":"2009","unstructured":"Bock F, Onderka J, Rummelt C, Dietrich T, Bachmann B, Kruse FE, Schl\u00f6tzer\u2010Schrehardt U, Cursiefen C (2009) Safety profile of topical VEGF neutralization at the cornea. 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