Parang Bobak, Thompson Joshua J, Williams Christopher S
a Department of Medicine , Cornell University , New York , NY , USA.
b Department of Medicine, Division of Gastroenterology , Vanderbilt University , Nashville , TN , USA.
Tissue Barriers. 2018;6(4):1-12. doi: 10.1080/21688370.2018.1499843. Epub 2018 Oct 11.
Blood vessel epicardial substance (BVES) is a tight-junction associated protein that was originally discovered from a cDNA screen of the developing heart. Research over the last decade has shown that not only is BVES is expressed in cardiac and skeletal tissue, but BVES is also is expressed throughout the gastrointestinal epithelium. Mice lacking BVES sustain worse intestinal injury and inflammation. Furthermore, BVES is suppressed in gastrointestinal cancers, and mouse modeling has shown that loss of BVES promotes tumor formation. Recent work from multiple laboratories has revealed that BVES can regulate several molecular pathways, including cAMP, WNT, and promoting the degradation of the oncogene, c-Myc. This review will summarize our current understanding of how BVES regulates the intestinal epithelium and discuss how BVES functions at the molecular level to preserve epithelial phenotypes and suppress tumorigenesis.
血管心外膜物质(BVES)是一种与紧密连接相关的蛋白质,最初是从发育中心脏的cDNA筛选中发现的。过去十年的研究表明,BVES不仅在心脏和骨骼肌组织中表达,还在整个胃肠道上皮中表达。缺乏BVES的小鼠肠道损伤和炎症更严重。此外,BVES在胃肠道癌症中受到抑制,小鼠模型表明BVES的缺失会促进肿瘤形成。多个实验室最近的研究表明,BVES可以调节多种分子途径,包括cAMP、WNT,并促进癌基因c-Myc的降解。本综述将总结我们目前对BVES如何调节肠道上皮的理解,并讨论BVES在分子水平上如何发挥作用以维持上皮表型并抑制肿瘤发生。