| First Author | Xie H | Year | 2022 |
| Journal | Exp Cell Res | Volume | 411 |
| Issue | 2 | Pages | 113003 |
| PubMed ID | 34979108 | Mgi Jnum | J:319878 |
| Mgi Id | MGI:6865406 | Doi | 10.1016/j.yexcr.2021.113003 |
| Citation | Xie H, et al. (2022) Integrin alphavbeta6 contributes to the development of intestinal fibrosis via the FAK/AKT signaling pathway. Exp Cell Res 411(2):113003 |
| abstractText | Intestinal fibrosis is one of the most severe complications of inflammatory bowel disease (IBD) and frequently requires surgery due to intestinal obstruction. Integrin alphavbeta6, which is mainly regulated by the integrin beta6 subunit gene (ITGB6), is a special integrin subtype expressed only in epithelial cells. In our previous study, we found integrin alphavbeta6 can promote the development of IBD, but the role of integrin alphavbeta6 in intestinal fibrosis remains unclear. In this study, we observed a gradual increase of ITGB6 mRNA expression from normal region to stenotic region of IBD patients' intestinal specimens. Next, we established a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and a heterotopic intestinal transplant model, and found intestinal fibrosis was decreased in ITGB6-deficient mice compared to wild-type (WT) mice. Furthermore, we performed RNA-sequencing and KEGG pathway analysis on intestinal tissues from ITGB6-overexpressing transgenic mice and WT mice, and found multiple pathways containing ITGB6, are related to the activation of focal adhesion kinase (FAK); finding was confirmed by Western blot. At last, we generated a heterotopic intestinal transplant model found the FAK/AKT pathway was inhibited in ITGB6-deficient mice. In conclusion, our data demonstrate that integrin alphavbeta6 promotes the pathogenesis of intestinal fibrosis by FAK/AKT pathway, making integrin alphavbeta6 a potential therapeutic target to prevent this condition. |
