ArticleEMBO molecular medicine2022
SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- COVID-19, the disease that changed the world.Medicine and pharmacy reports · 2026Review
- Clinical features, treatments and prognosis of COVID-19 (Omicron) and hemorrhagic colitis: a case series study.BMC gastroenterology · 2025Article
- Increase of VEGF and Fibronectin expression and ultrastructural alterations of intercellular junctions in a swab negative patient after SARS-COV-2 infection.Virology journal · 2025Article
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- COVID-19 vaccination, all-cause mortality, and hospitalization for cancer: 30-month cohort study in an Italian province.EXCLI journal · 2025Article
- Overview of the Trending Enteric Viruses and Their Pathogenesis in Intestinal Epithelial Cell Infection.Biomedicines · 2024Review
- Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine.The EMBO journal · 2024Article
- Review
- Single-cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism-related mechanisms.Clinical and translational medicine · 2024Article
- Article
- TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression.Cell death & disease · 2024Article
- SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike-induced intestinal inflammation.Precision clinical medicine · 2024Article
- Spatial immune landscapes of SARS-CoV-2 gastrointestinal infection: macrophages contribute to local tissue inflammation and gastrointestinal symptoms.Frontiers in cell and developmental biology · 2024Article
- Multifaceted role of SARS-CoV-2 structural proteins in lung injury.Frontiers in immunology · 2024Review
- SARS-Cov-2 spike induces intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9.Frontiers in immunology · 2024Article
- Review
- Organoids to Remodel SARS-CoV-2 Research: Updates, Limitations and Perspectives.Aging and disease · 2023Review
- Development and management of gastrointestinal symptoms in long-term COVID-19.Frontiers in microbiology · 2023Review
- SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes.EMBO molecular medicine · 2022Article
- Microbiota and COVID-19: Long-term and complex influencing factors.Frontiers in microbiology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. 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-CoV-2 spike protein, we further revealed that VEGF was over-produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS-CoV-2 spike promoted VEGF production through activating the Ras-Raf-MEK-ERK 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 in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID-19.
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Registered trials
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