SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes
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 pat...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2022-05-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202114844 |
| _version_ | 1797287309429702656 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fa‐Min Zeng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T18:31:08Z |
| format | Article |
| id | doaj.art-842c9638bc184dcebd6ba7b980a830fe |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T18:31:08Z |
| publishDate | 2022-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-842c9638bc184dcebd6ba7b980a830fe2024-03-02T06:26:27ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-05-01145n/an/a10.15252/emmm.202114844SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytesFa‐Min Zeng0Ying‐wen Li1Zhao‐hua Deng2Jian‐zhong He3Wei Li4Lijie Wang5Ting Lyu6Zhanyu Li7Chaoming Mei8Meiling Yang9Yingying Dong10Guan‐Min Jiang11Xiaofeng Li12Xi Huang13Fei Xiao14Ye Liu15Hong Shan16Huanhuan He17Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Pathology The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Pathology The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Pathology The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Pathology The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Clinical Laboratory The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Gastroenterology The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Infectious Diseases The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaDepartment of Pathology The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat‐sen University Zhuhai ChinaAbstract 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.https://doi.org/10.15252/emmm.202114844COVID‐19GI symptomsintestinal inflammationvascular permeabilityVEGF |
| spellingShingle | 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 SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes EMBO Molecular Medicine COVID‐19 GI symptoms intestinal inflammation vascular permeability VEGF |
| title | SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes |
| title_full | SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes |
| title_fullStr | SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes |
| title_full_unstemmed | SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes |
| title_short | SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes |
| title_sort | sars cov 2 spike spurs intestinal inflammation via vegf production in enterocytes |
| topic | COVID‐19 GI symptoms intestinal inflammation vascular permeability VEGF |
| url | https://doi.org/10.15252/emmm.202114844 |
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