PEDV infection downregulates goblet cell differentiation through activating the Notch pathway
Abstract Porcine epidemic diarrhoea virus (PEDV) is the most widespread porcine coronavirus worldwide, causing high mortality and a high incidence rate among piglets. The molecular mechanisms by which PEDV regulates epithelial cell function and differentiation, as well as its disruption of the intes...
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| Language: | English |
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BMC
2025-08-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-025-01599-5 |
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| author | Yi Wang Shanshan Yang Yongxiang Zhao Shuo Tian Qiuxia Cao Xinmei Geng Mengdi Yang Xu Song Hongqi Shang Shiyu Liu Rongli Guo Yunchuan Li Min Sun Mi Hu Baochao Fan Bin Li |
| author_facet | Yi Wang Shanshan Yang Yongxiang Zhao Shuo Tian Qiuxia Cao Xinmei Geng Mengdi Yang Xu Song Hongqi Shang Shiyu Liu Rongli Guo Yunchuan Li Min Sun Mi Hu Baochao Fan Bin Li |
| author_sort | Yi Wang |
| collection | DOAJ |
| description | Abstract Porcine epidemic diarrhoea virus (PEDV) is the most widespread porcine coronavirus worldwide, causing high mortality and a high incidence rate among piglets. The molecular mechanisms by which PEDV regulates epithelial cell function and differentiation, as well as its disruption of the intestinal mucosal barrier, are not yet fully understood. This study reveals that PEDV infection reduces the number of goblet cells and impairs the intestinal barrier integrity in newborn piglets. Regarding the pathways involved in the differentiation of intestinal stem cells (ISCs), PEDV infection concurrently activates the Notch and MAPK pathways while suppressing the Wnt/β-catenin pathway in the intestines of piglets. Furthermore, in vitro experiments using intestinal monolayer organoid models showed that PEDV infection hinders goblet cell differentiation by activating the Notch signalling pathway. Additionally, the PEDV-encoded ORF3 protein, which is crucial for activating the Notch pathway, inhibits goblet cell differentiation in PEDV-infected intestinal monolayer organoids. This study offers new insights into the mechanisms underlying intestinal mucosal barrier dysfunction induced by PEDV infection. |
| format | Article |
| id | doaj-art-d7a6c031ab814bbbabeff655444b4c29 |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-d7a6c031ab814bbbabeff655444b4c292025-08-20T03:46:29ZengBMCVeterinary Research1297-97162025-08-0156111210.1186/s13567-025-01599-5PEDV infection downregulates goblet cell differentiation through activating the Notch pathwayYi Wang0Shanshan Yang1Yongxiang Zhao2Shuo Tian3Qiuxia Cao4Xinmei Geng5Mengdi Yang6Xu Song7Hongqi Shang8Shiyu Liu9Rongli Guo10Yunchuan Li11Min Sun12Mi Hu13Baochao Fan14Bin Li15School of Veterinary Medicine, Hebei Agricultural UniversityInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesSchool of Veterinary Medicine, Hebei Agricultural UniversityInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesInstitute of Veterinary Medicine, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural SciencesSchool of Veterinary Medicine, Hebei Agricultural UniversityAbstract Porcine epidemic diarrhoea virus (PEDV) is the most widespread porcine coronavirus worldwide, causing high mortality and a high incidence rate among piglets. The molecular mechanisms by which PEDV regulates epithelial cell function and differentiation, as well as its disruption of the intestinal mucosal barrier, are not yet fully understood. This study reveals that PEDV infection reduces the number of goblet cells and impairs the intestinal barrier integrity in newborn piglets. Regarding the pathways involved in the differentiation of intestinal stem cells (ISCs), PEDV infection concurrently activates the Notch and MAPK pathways while suppressing the Wnt/β-catenin pathway in the intestines of piglets. Furthermore, in vitro experiments using intestinal monolayer organoid models showed that PEDV infection hinders goblet cell differentiation by activating the Notch signalling pathway. Additionally, the PEDV-encoded ORF3 protein, which is crucial for activating the Notch pathway, inhibits goblet cell differentiation in PEDV-infected intestinal monolayer organoids. This study offers new insights into the mechanisms underlying intestinal mucosal barrier dysfunction induced by PEDV infection.https://doi.org/10.1186/s13567-025-01599-5PEDVNotch signalling pathwaygoblet cellsORF3intestinal organoids |
| spellingShingle | Yi Wang Shanshan Yang Yongxiang Zhao Shuo Tian Qiuxia Cao Xinmei Geng Mengdi Yang Xu Song Hongqi Shang Shiyu Liu Rongli Guo Yunchuan Li Min Sun Mi Hu Baochao Fan Bin Li PEDV infection downregulates goblet cell differentiation through activating the Notch pathway Veterinary Research PEDV Notch signalling pathway goblet cells ORF3 intestinal organoids |
| title | PEDV infection downregulates goblet cell differentiation through activating the Notch pathway |
| title_full | PEDV infection downregulates goblet cell differentiation through activating the Notch pathway |
| title_fullStr | PEDV infection downregulates goblet cell differentiation through activating the Notch pathway |
| title_full_unstemmed | PEDV infection downregulates goblet cell differentiation through activating the Notch pathway |
| title_short | PEDV infection downregulates goblet cell differentiation through activating the Notch pathway |
| title_sort | pedv infection downregulates goblet cell differentiation through activating the notch pathway |
| topic | PEDV Notch signalling pathway goblet cells ORF3 intestinal organoids |
| url | https://doi.org/10.1186/s13567-025-01599-5 |
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