Mechanisms of action studies of WBI-4002, a novel drug candidate promoting epithelial integrity

我们的组织表面与环境接触的细胞被称为上皮细胞。为了形成屏障，上皮细胞彼此紧密相连，有时堆叠在一起，就像我们的皮肤一样。在肠道中，为了消化和吸收食物，上皮只有一个细胞厚。结果是，“紧密性”可以被宿主体内的事件或到达管腔的产物所改变。在乳糜泻、克罗恩病和溃疡性结肠炎等疾病中，会发生这些“紧密性”或完整性的变化。虽然我们了解与上皮完整性相关的分子，但我们没有很多产品可以在需要时改善它，但我们从食物中得到了一些线索。我们饮食中的某些植物被认为具有抗炎和抗氧化的特性（例如蓝莓）。当科学家们努力提纯活性植物产品时，“多酚二苯乙烯”被发现对健康有益。Welichem Biotech Inc. （Burnaby， BC）开发了一种名为WBI-4002的此类药物。WBI-4002是一种反式羟基苯乙烯。他们已经了解到，这种药物与细胞表面的一种叫做芳烃受体（AhR）的分子结合。AhR存在于许多类型的细胞中，包括上皮细胞。其他研究人员表明，当AhR结合相容分子时，它可以改善上皮的完整性。Welichem生物技术公司想知道他们的药物是否也能改变上皮的完整性。公司联系了斯塔德尼克博士，他是肠上皮的专家。Stadnyk博士将把WBI-4002应用于培养皿中人类和小鼠的肠上皮细胞，并测量其对完整性的影响。他将检查构成细胞间键的分子，以弄清楚当WBI0-4002应用时发生了什么变化。如果这种药物能改善上皮的完整性，它可能是治疗肠道炎症性疾病的一个很好的候选药物。

The cells lining our tissue surfaces in contact with the environment are called epithelial cells. To create a barrier epithelial cells are tightly connected to each other and are sometimes stacked upon each other, like on our skin. In the intestines the epithelium is only one cell thick in order to digest and absorb food. The result is that the "tightness" can be modified by events in the host or from products arriving in the lumen. These changes in "tightness" or integrity occur during diseases like Celiac disease or Crohn's disease and ulcerative colitis. While we understand the molecules involved in epithelial integrity we don't have many products that can improve it when we may need to, but we have some clues from our the food. Certain plants in our diet are thought to have anti-inflammatory and anti-oxidant properties (blueberries, for example). As scientists worked to purify the active plant products "polyphenol stilbenes" were discovered to have health benefits. Welichem Biotech Inc. (Burnaby, BC) has developed a drug in this class they call WBI-4002. WBI-4002 is a trans-hydroxystilbene. They have learned that the drug binds a molecule on the surface of cells called the aryl hydrocarbon receptor (AhR). The AhR is present on many types of cells including on epithelial cells. Other researchers showed that when the AhR binds compatible molecules it can improve the integrity of the epithelium. Welichem Biotech Inc. wants to know if their drug can also modify the integrity of epithelium. The Company contacted Dr. Stadnyk, who is an expert on the intestinal epithelium. Dr. Stadnyk will apply WBI-4002 to intestinal epithelial cells, from humans and mice, in petri dishes, and measure any effects on integrity. He will examine the molecules that make up the bonds between cells to figure out what changes when WBI0-4002 is applied. If the drug works to improve epithelial integrity it may be a good candidate for treating inflammatory diseases of the intestines.