Ephrin B3 exacerbates colitis and colitis-associated colorectal cancer

  • Impact factors: 5.8
  • Publication: BIOCHEMICAL PHARMACOLOGY
  • Author:Zhen Qiao, Min Liao, Mingyue Xiao, Saiyan Luo, Kexin Wang, Mengxin Niu, Honglv Jiang, Suya Sun, Guoqiang Xu, NanJie Xu, Qiongming Xu, Yanli Liu
  • DOI citation-doi:10.1016/j.bcp.2023.116004
  • Date:2023-12-22

Ephrin B3 , a member of Eph/ephrin family, contributes to embryogenesis and carcinogenesis, but few studies have suggested whether this ligand has regulatory effect on colitis . This study was to determine whether ephrin B3 played a role in colitis and colonic carcinogenesis. Dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated carcinogenesis model was established in Efnb3 -deficient ( Efnb3 −/− ) mice. Label-free quantitative proteomics were performed to identify the Efnb3- regulated proteins. Our results showed that Efnb3 knock out reduced the symptoms of DSS-induced colitis, such as disease activity index (DAI), inflammatory factors release, and dysfunction of the intestinal barrier. Quantitative proteomics revealed that Efnb3 regulated 95 proteins which clustered in the platelet degranulation, response to elevated platelet cytosolic Ca 2+ , MAPK signaling for integrins such as ITGB4. Furthermore, ephrin B3 inactived ITGB4/AKT signal pathway and then promoted epithelial barrier dysfunction. Simultaneously, ephrin B3 promoted Gremlin-1/NF-κB signal pathway and thereby increased inflammatory factors release. In addition, the higher level of Efnb3 in colon cancer patients is correlated with worse survival. Efnb3 −/− mice exhibited susceptibility to AOM/DSS-induced colorectal cancer . Our finding discovered that Efnb3 played an important role in the development of colitis and colitis-associated colorectal cancer. Efnb3 deficiency improved the intestinal barrier by ITGB4 and suppressed inflammation via Gremlin-1/NF-κB signal pathway, which may provide a novel therapeutic strategy for the treatment of colitis and colitis-associated colorectal cancer.

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