Leppänen Joni, Helminen Olli, Huhta Heikki, Kauppila Joonas H, Miinalainen Ilkka, Ronkainen Veli-Pekka, Saarnio Juha, Lehenkari Petri P, Karttunen Tuomo J
Department of Pathology, University of Oulu, Oulu, Finland.
Department of Surgery, University of Oulu, Oulu, Finland.
APMIS. 2016 Nov;124(11):958-965. doi: 10.1111/apm.12599. Epub 2016 Sep 28.
Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated kinase. In murine intestine, DCLK1 marks tuft cells with characteristic microvilli, features of neuroendocrine cells and also quiescent stem cell-like properties. The occurrence and pathological role of DCLK1-positive cells in human intestinal mucosa is unknown. We analysed DCLK1 expression in healthy duodenal, jejunal and colorectal mucosa samples (n = 35), and in duodenal specimens from patients with coeliac disease (n = 20). The samples were immunohistochemically double-stained with DCLK1, and synaptophysin, chromogranin A and Ki-67. Ultrastructure of DCLK1-expressing duodenal cells was assessed using correlative light and electron microscopy. DCLK1 expression was seen in about 1% of epithelial cells diffusely scattered through the intestinal epithelium. Electron microscopy showed that the duodenal DCLK1-positive cells had short apical microvilli similar to neighbouring enterocytes and cytoplasmic granules on the basal side. DCLK1-positive cells were stained with synaptophysin. The number of DCLK1-positive cells was decreased in villus atrophy in coeliac disease. Our findings indicate that in human intestinal epithelium, DLCK1-positive cells form a subpopulation of non-proliferating neuroendocrine cells with apical brush border similar to that in enterocytes, and their number is decreased in untreated coeliac disease.
双皮质素样激酶1(DCLK1)是一种微管相关激酶。在小鼠肠道中,DCLK1标记具有特征性微绒毛的簇状细胞、神经内分泌细胞特征以及静止干细胞样特性。DCLK1阳性细胞在人肠黏膜中的发生情况及病理作用尚不清楚。我们分析了健康十二指肠、空肠和结肠黏膜样本(n = 35)以及乳糜泻患者十二指肠标本(n = 20)中DCLK1的表达。样本用DCLK1、突触素、嗜铬粒蛋白A和Ki-67进行免疫组织化学双重染色。使用相关光镜和电镜评估表达DCLK1的十二指肠细胞的超微结构。在约1%弥漫性散在于肠上皮的上皮细胞中可见DCLK1表达。电镜显示十二指肠DCLK1阳性细胞具有与相邻肠上皮细胞相似的短顶端微绒毛以及基底侧的细胞质颗粒。DCLK1阳性细胞被突触素染色。乳糜泻绒毛萎缩时DCLK1阳性细胞数量减少。我们的研究结果表明,在人肠上皮中,DLCK1阳性细胞形成一个非增殖性神经内分泌细胞亚群,其顶端刷状缘与肠上皮细胞相似,且在未经治疗的乳糜泻中其数量减少。