SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes

Autor: Fa‐Min Zeng, Ying‐wen Li, Zhao‐hua Deng, Jian‐zhong He, Wei Li, Lijie Wang, Ting Lyu, Zhanyu Li, Chaoming Mei, Meiling Yang, Yingying Dong, Guan‐Min Jiang, Xiaofeng Li, Xi Huang, Fei Xiao, Ye Liu, Hong Shan, Huanhuan He
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 14, Iss 5, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202114844
Popis: 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.
Databáze: Directory of Open Access Journals
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