Abstract:
The lectin TFF2 belongs to the trefoil factor family (TFF). This polypeptide is typically co-secreted with the mucin MUC6 from gastric mucous neck cells, antral gland cells, and duodenal Brunner glands. Here, TFF2 fulfills a protective function by forming a high-molecular-mass complex with the MUC6, physically stabilizing the mucus barrier. In pigs and mice, and slightly in humans, TFF2 is also synthesized in the pancreas. Here, we investigated the murine stomach, pancreas, and duodenum by fast protein liquid chromatography (FPLC) and proteomics and identified different forms of Tff2. In both the stomach and duodenum, the predominant form is a high-molecular-mass complex with Muc6, whereas, in the pancreas, only low-molecular-mass monomeric Tff2 was detectable. We also investigated the expression of Tff2 and other selected genes in the stomach, pancreas, and the proximal, medial, and distal duodenum (RT-PCR analysis). The absence of the Tff2/Muc6 complex in the pancreas is due to a lack of Muc6. Based on its known motogenic, anti-apoptotic, and anti-inflammatory effects, we propose a protective receptor-mediated function of monomeric Tff2 for the pancreatic ductal epithelium. This view is supported by a report that a loss of Tff2 promotes the formation of pancreatic intraductal mucinous neoplasms.
摘要:
凝集素TFF2属于三叶因子家族(TFF)。该多肽通常与来自胃粘膜颈细胞的粘蛋白MUC6共同分泌,窦腺细胞,和十二指肠Brunner腺体。这里,TFF2通过与MUC6形成高分子质量复合物,物理稳定粘液屏障来实现保护功能。在猪和老鼠身上,在人类中,TFF2也在胰腺中合成。这里,我们调查了鼠的胃,胰腺,通过快速蛋白液相色谱(FPLC)和蛋白质组学等方法鉴定了不同形式的Tff2。在胃和十二指肠,主要形式是具有Muc6的高分子量复合物,而,在胰腺里,只有低分子质量的单体Tff2被检测到。我们还研究了Tff2和其他选定基因在胃中的表达,胰腺,和近端,中间,和远端十二指肠(RT-PCR分析)。胰腺中不存在Tff2/Muc6复合物是由于缺乏Muc6。根据其已知的动机,抗凋亡,和抗炎作用,我们提出了Tff2单体对胰腺导管上皮的保护性受体介导的功能。Tff2的丢失促进胰腺导管内粘液性肿瘤的形成的报道支持了这一观点。