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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-08-01
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.
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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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