文献类型： 外文期刊

作者： Yang, Ning ¹ ; Zhang, Yunhang ¹ ; Fu, Yuguang ¹ ; Li, Yang ¹ ; Yang, Shanshan ¹ ; Chen, Jianing ¹ ; Liu, Guangliang ¹ ;

作者机构： 1.Lanzhou Univ, Chinese Acad Agr Sci, Coll Vet Med, Lanzhou Vet Res Inst,State Key Lab Vet Etiol Biol, Lanzhou, Peoples R China

2.Univ Liege, Mol & Cellular Epigenet GIGA, Gembloux, Belgium

3.Univ Liege, Mol Biol TERRA, Gembloux, Belgium

4.Hainan Acad Agr Sci, Inst Anim Husb & Vet Med, Hainan Key Lab Trop Anim Breeding & Infect Dis Re, Haikou, Hainan, Peoples R China

5.Wageningen Univ & Res, Cell Biol & Immunol Grp, Wageningen, Netherlands

关键词： TGEV; Wnt/beta-catenin pathway; epithelium regeneration; intestinal organoid monolayer; intestinal stem cells

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：6.549； 五年影响因子：5.78 ）

ISSN： 0022-538X

年卷期： 2022 年 96 卷 18 期

页码：

收录情况： SCI

摘要： 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/beta-catenin pathway by upregulating the accumulation and nuclear translocation of beta-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 selfrenewal of ISCs. Collectively, these data demonstrated that the TGEV infection activated the Wnt/beta-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/beta-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.