Abstract:
Tff1 is a typical gastric peptide secreted together with the mucin, Muc5ac. Tff1-deficient (Tff1KO) mice are well known for their prominent gastric phenotype and represent a recognized model for antral tumorigenesis. Notably, intestinal abnormalities have also been reported in the past in these animals. Here, we have compared the expression of selected genes in Tff1KO mice and their corresponding wild-type littermates (RT-PCR analyses), focusing on different mucosal protection systems along the murine intestine. As hallmarks, genes were identified with maximum expression in the proximal colon and/or the duodenum: Agr2, Muc6/A4gnt/Tff2, Tff1, Fut2, Gkn2, Gkn3, Duox2/Lpo, Nox1. This is indicative of different protection systems such as Tff2/Muc6, Tff1-Fcgbp, gastrokines, fucosylation, and reactive oxygen species (ROS) in the proximal colon and/or duodenum. Few significant transcriptional changes were observed in the intestine of Tff1KO mice when compared with wild-type littermates, Clca1 (Gob5), Gkn1, Gkn2, Nox1, Tff2. We also analyzed the expression of Tff1, Tff2, and Tff3 in the pancreas, liver, and lung of Tff1KO and wild-type animals, indicating a cross-regulation of Tff gene expression. Furthermore, on the protein level, heteromeric Tff1-Fcgbp and various monomeric Tff1 forms were identified in the duodenum and a high-molecular-mass Tff2/Muc6 complex was identified in the proximal colon (FPLC, proteomics).
摘要:
Tff1是一种典型的胃肽,与粘蛋白一起分泌,Muc5ac.Tff1缺陷(Tff1KO)小鼠以其突出的胃表型而闻名,并代表了公认的胃窦肿瘤发生模型。值得注意的是,过去在这些动物中也有肠道异常的报道。这里,我们比较了Tff1KO小鼠及其相应的野生型同窝动物中选定基因的表达(RT-PCR分析),专注于鼠肠不同的粘膜保护系统。作为标志,在近端结肠和/或十二指肠中鉴定出最大表达的基因:Agr2,Muc6/A4gnt/Tff2,Tff1,Fut2,Gkn2,Gkn3,Duox2/Lpo,Nox1.这表明不同的保护系统,如Tff2/Muc6,Tff1-Fcgbp,腹肌,岩藻糖基化,和近端结肠和/或十二指肠中的活性氧(ROS)。与野生型同窝相比,在Tff1KO小鼠的肠道中几乎没有观察到显着的转录变化,Clca1(Gob5),Gkn1,Gkn2,Nox1,Tff2.我们还分析了Tff1,Tff2和Tff3在胰腺中的表达,肝脏,Tff1KO和野生型动物的肺,表明Tff基因表达的交叉调节。此外,在蛋白质水平上,在十二指肠中鉴定出异聚Tff1-Fcgbp和各种单体Tff1形式,并且在近端结肠中鉴定出高分子质量的Tff2/Muc6复合物(FPLC,蛋白质组学)。