tetano
Editor, Senior Moderator
EMBO Mol Med
. 2022 Mar 31;e14844.
doi: 10.15252/emmm.202114844. Online ahead of print.
SARS-CoV-2 Spike Spurs Intestinal Inflammation via VEGF Production in Enterocytes
Fa-Min Zeng[SUP] 1 2 [/SUP], Ying-Wen Li[SUP] 1 [/SUP], Zhao-Hua Deng[SUP] 1 [/SUP], Jian-Zhong He[SUP] 2 [/SUP], Wei Li[SUP] 2 [/SUP], Lijie Wang[SUP] 1 [/SUP], Ting Lyu[SUP] 2 [/SUP], Zhanyu Li[SUP] 2 [/SUP], Chaoming Mei[SUP] 1 [/SUP], Meiling Yang[SUP] 1 [/SUP], Ying-Ying Dong[SUP] 1 [/SUP], Guan-Min Jiang[SUP] 3 [/SUP], Xiaofeng Li[SUP] 4 [/SUP], Xi Huang[SUP] 5 [/SUP], Fei Xiao[SUP] 1 5 [/SUP], Ye Liu[SUP] 2 [/SUP], Hong Shan[SUP] 1 6 [/SUP], Huanhuan He[SUP] 1 [/SUP]
Affiliations
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. Serum 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.
Keywords: COVID-19; GI symptoms; Intestinal inflammation; VEGF; Vascular permeability.
. 2022 Mar 31;e14844.
doi: 10.15252/emmm.202114844. Online ahead of print.
SARS-CoV-2 Spike Spurs Intestinal Inflammation via VEGF Production in Enterocytes
Fa-Min Zeng[SUP] 1 2 [/SUP], Ying-Wen Li[SUP] 1 [/SUP], Zhao-Hua Deng[SUP] 1 [/SUP], Jian-Zhong He[SUP] 2 [/SUP], Wei Li[SUP] 2 [/SUP], Lijie Wang[SUP] 1 [/SUP], Ting Lyu[SUP] 2 [/SUP], Zhanyu Li[SUP] 2 [/SUP], Chaoming Mei[SUP] 1 [/SUP], Meiling Yang[SUP] 1 [/SUP], Ying-Ying Dong[SUP] 1 [/SUP], Guan-Min Jiang[SUP] 3 [/SUP], Xiaofeng Li[SUP] 4 [/SUP], Xi Huang[SUP] 5 [/SUP], Fei Xiao[SUP] 1 5 [/SUP], Ye Liu[SUP] 2 [/SUP], Hong Shan[SUP] 1 6 [/SUP], Huanhuan He[SUP] 1 [/SUP]
Affiliations
- PMID: 35362189
- DOI: 10.15252/emmm.202114844
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. Serum 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.
Keywords: COVID-19; GI symptoms; Intestinal inflammation; VEGF; Vascular permeability.