Differences in goblet cell differentiation between Crohn's disease and ulcerative colitis
Differences in goblet cell differentiation between Crohn's disease and ulcerative colitis
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DOI：
10.1016/j.diff.2008.09.008
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发表时间：
2009-01-01
期刊：
影响因子：
2.9
通讯作者：
Stange, Eduard Friedrich
中科院分区：
文献类型：
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作者：
Gersemann, Michael;Becker, Svetlana;Stange, Eduard Friedrich
杯状细胞是分泌粘蛋白的肠细胞，形成保护粘膜表面的粘液层。溃疡性结肠炎（UC）与结肠粘液层缺陷和杯状细胞数量减少有关。在实验动物中，结肠杯状细胞分化受到相互作用的转录因子 Hath1、KLF4 和 Notch 以及 Wnt 通路的调节，而人类的数据有限。我们研究了对照组和炎症性肠病 (IBD) 中的杯状细胞分化因子和粘蛋白。我们对 Hath1、KLF4、Notch 和 Wnt 通路的几种配体、受体和靶基因，以及来自对照 (n = 21)、克罗恩病 (CD，n = 48) 和 UC (n = 40) 乙状结肠活检中的几种粘蛋白进行了实时 PCR。此外，通过蛋白质印迹对 Hath1 蛋白进行定量，并通过免疫组织化学进行定位。值得注意的是，两种疾病实体中通过 IL-8 和组织学测量的炎症程度相似。两种 IBD 中杯状细胞的比例均降低，但在 UC 中隐窝上三分之一处的杯状细胞比例明显减少。相当水平的炎症诱导了 Hath1（2.0 倍，p
Goblet cells are mucin-secreting intestinal cells forming the mucus layer that protects the mucosal surface. Ulcerative colitis (UC) has been associated with a defective colonic mucus layer and a reduced number of goblet cells. In experimental animals, colonic goblet cell differentiation is regulated by interacting transcription factors Hath1, KLF4 and the Notch, as well as Wnt pathways, whereas data in humans are limited. We investigated goblet cell differentiation factors and mucins in controls and in inflammatory bowel diseases (IBDs). We performed real-time PCR for Hath1, KLF4, several ligands, receptors and target genes of the Notch and Wnt pathways, as well as several mucins in biopsies from the sigmoid colon of controls (n = 21), Crohn's disease (CD, n = 48) and UC (n = 40). In addition, Hath1 protein was quantitated with Western blot and localized with immunohistochemistry. Notably, the degree of inflammation as measured by IL-8 and histology was similar in both disease entities. The proportion of goblet cells was lowered in both IBDs, but specifically diminished in the upper third of the crypt in UC. Comparable levels of inflammation induced both Hath1 (2.0-fold, p