[en] Intestinal stem cells (ISCs) play an important role in tissue repair after injury. A recent report delineates the effect of transmissible gastroenteritis virus (TGEV) infection on the small intestine of recovered pigs. However, the mechanism behind the epithelium regeneration upon TGEV infection remains unclear. To address this, we established a TGEV infection model based on the porcine intestinal organoid monolayer. The results illustrated that the porcine intestinal organoid monolayer was susceptible to TGEV. In addition, the TGEV infection initiated the interferon and inflammatory responses following the loss of absorptive enterocytes and goblet cells. However, TGEV infection did not disturb epithelial integrity but induced the proliferation of ISCs. Furthermore, TGEV infection activated the Wnt/β-catenin pathway by upregulating the accumulation and nuclear translocation of β-catenin, as well as promoting the expression of Wnt target genes, such as C-myc, Cyclin D1, Mmp7, Lgr5, and Sox9, which were associated with the self-renewal of ISCs. Collectively, these data demonstrated that the TGEV infection activated the Wnt/β-catenin pathway to promote the self-renewal of ISCs and resulted in intestinal epithelium regeneration. IMPORTANCE The intestinal epithelium is a physical barrier to enteric viruses and commensal bacteria. It plays an essential role in maintaining the balance between the host and intestinal microenvironment. In addition, intestinal stem cells (ISCs) are responsible for tissue repair after injury. Therefore, prompt self-renewal of intestinal epithelium will facilitate the rebuilding of the physical barrier and maintain gut health. In the manuscript, we found that the transmissible gastroenteritis virus (TGEV) infection did not disturb epithelial integrity but induced the proliferation of ISCs and facilitated epithelium regeneration. Detailed mechanism investigations revealed that the TGEV infection activated the Wnt/β-catenin pathway to promote the self-renewal of ISCs and resulted in intestinal epithelium regeneration. These findings will contribute to understanding the mechanism of intestinal epithelial regeneration and reparation upon viral infection.
Disciplines :
Biotechnology
Author, co-author :
Yang, Ning ; Université de Liège - ULiège > TERRA Research Centre ; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China
Zhang, Yunhang ; Université de Liège - ULiège > TERRA Research Centre ; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China
Fu, Yuguang; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China
Li, Yang ; Université de Liège - ULiège > Université de Liège - ULiège ; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China
Yang, Shanshan; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China ; Cell Biology and Immunology Group, Wageningen University and Research, Wageningen, The Netherlands
Chen, Jianing; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China
Liu, Guangliang ; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institutegrid.454892.6, Chinese Academy of Agricultural Sciences, Lanzhou, China ; Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China
Language :
English
Title :
Transmissible Gastroenteritis Virus Infection Promotes the Self-Renewal of Porcine Intestinal Stem Cells via Wnt/β-Catenin Pathway.
NSCF - National Natural Science Foundation of China
Funding text :
We thank Li Feng from Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences for providing a TGEV monoclonal antibody. This work was supported by the National Natural Science Foundation of China (31972689) and ULg-CAAS joint Ph.D. Program.
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