Lennicke Claudia, Rahn Jette, Wickenhauser Claudia, Lichtenfels Rudolf, Müller Andreas S, Wessjohann Ludger A, Kipp Anna P, Seliger Barbara
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
Institute of Pathology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
Oncotarget. 2017 Nov 23;9(1):539-552. doi: 10.18632/oncotarget.22640. eCollection 2018 Jan 2.
The selenoprotein glutathione peroxidase 2 (GPx2) is expressed in the epithelium of the gastrointestinal tract, where it is thought to be involved in maintaining mucosal homeostasis. To gain novel insights into the role of GPx2, proteomic profiles of colonic tissues either derived from wild type (WT) or GPx2 knockout (KO) mice, maintained under selenium (Se) deficiency or adequate Se supplementation conditions were established and analyzed. Amongst the panel of differentially expressed proteins, the calcium-activated chloride channel regulator 1 (CLCA1) was significantly down-regulated in GPx2 KO versus WT mice regardless of the given Se status. Moreover, transcript levels of the isoforms CLCA2 and CLCA3 showed a similar expression pattern. In the intestine, CLCA1 is usually restricted to mucin-producing goblet cells. However, although -SeKO mice had the highest numbers of goblet cells as confirmed by significantly enhanced mRNA expression levels of the goblet cell marker mucin-2, the observed expression pattern suggests that GPx2 KO goblet cells might be limited in synthesizing CLCA1. Furthermore, transcript levels of differentiation markers such as chromogranin-1 (Chga) for enteroendocrine cells and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) for stem cells were also downregulated in GPx2 KO mice. Moreover, this was accompanied by a downregulation of the mRNA expression levels of the intestinal hormones glucagon-like peptide 1 (Glp1), ghrelin (Ghrl) and somatostatin (Sst). Thus, it seems that GPx2 might be important for the modulation of cell fate decisions in the murine intestinal epithelium.
硒蛋白谷胱甘肽过氧化物酶2（GPx2）在胃肠道上皮中表达，据认为它参与维持黏膜稳态。为了深入了解GPx2的作用，我们建立并分析了在硒（Se）缺乏或充足硒补充条件下饲养的野生型（WT）或GPx2基因敲除（KO）小鼠结肠组织的蛋白质组学图谱。在差异表达蛋白质组中，无论硒状态如何，钙激活氯离子通道调节因子1（CLCA1）在GPx2基因敲除小鼠中相对于野生型小鼠均显著下调。此外，CLCA2和CLCA3亚型的转录水平显示出相似的表达模式。在肠道中，CLCA1通常局限于产生粘蛋白的杯状细胞。然而，尽管-硒缺乏基因敲除小鼠杯状细胞数量最多，杯状细胞标志物粘蛋白-2的mRNA表达水平显著提高证实了这一点，但观察到的表达模式表明，GPx2基因敲除的杯状细胞在合成CLCA1方面可能受到限制。此外，肠内分泌细胞的分化标志物嗜铬粒蛋白-1（Chga）和干细胞的富含亮氨酸重复序列的G蛋白偶联受体5（Lgr5）的转录水平在GPx2基因敲除小鼠中也下调。此外，这还伴随着肠道激素胰高血糖素样肽1（Glp1）、胃饥饿素（Ghrl）和生长抑素（Sst）的mRNA表达水平下调。因此，GPx2似乎对调节小鼠肠道上皮细胞命运决定很重要。
