Kouznetsova Irina, Laubinger Werner, Kalbacher Hubert, Kalinski Thomas, Meyer Frank, Roessner Albert, Hoffmann Werner
IInstitut fur Molekularbiologie und Medizinische Chemie,Otto-von-Guericke-Universitat Magdeburg, Magdeburg, Germany.
Cell Physiol Biochem. 2007;20(6):899-908. doi: 10.1159/000110450.
Gastrokine-2 (GKN2) is a secretory peptide of human gastric surface mucous cells (SMCs). It forms disulfide-linked heterodimers with the trefoil factor family (TFF) peptide TFF1. Binding with TFF2 was also reported. Antral SMCs differ from those of the corpus by their TFF3 expression. The aim of this study was to localize GKN2 expression along the antral gland axis, to characterize the continuous regeneration of antral glands, and to investigate the interactions of GKN2 with TFF1, TFF2 and mucins.
The spatial expression of GKN1, GKN2, TFF1-3, MUC5AC and MUC6 was determined using laser microdissection and RT-PCR analysis. Furthermore, antral extracts were separated by gel chromatography and the association of GKN2 with TFF1, TFF2, and mucins was investigated.
Differential GKN2 expression was localized along the rostro-caudal axis of the stomach. Laser microdissection revealed characteristic differential expression profiles of GKN1, GKN2, TFF1-3, MUC5AC and MUC6 along the antral gland axis. Both GKN2 and TFF1 were expressed in superficial SMCs. Surprisingly, the TFF1-GKN2 heterodimer did not associate with the mucin fraction; whereas TFF2 showed exclusive association with mucins.
Maturation of antral SMCs occurs stepwise via trans-differentiation of TFF3 expressing progenitor cells. The TFF1-GKN2 heterodimer and TFF2 differ characteristically by their binding to gastric mucins. This points to different physiological functions of TFF1 and TFF2, the latter maybe acting as a 'link peptide' for stabilization of the gastric mucus.
胃动素-2（GKN2）是人类胃表面黏液细胞（SMCs）分泌的一种肽。它与三叶因子家族（TFF）肽TFF1形成二硫键连接的异二聚体。也有报道称其与TFF2结合。胃窦部SMCs与胃体部的SMCs在TFF3表达上存在差异。本研究的目的是确定GKN2在胃窦腺轴上的表达定位，描述胃窦腺的持续再生特征，并研究GKN2与TFF1、TFF2和黏蛋白的相互作用。
使用激光显微切割和RT-PCR分析确定GKN1、GKN2、TFF1 - 3、MUC5AC和MUC6的空间表达。此外，通过凝胶色谱法分离胃窦提取物，并研究GKN2与TFF1、TFF2和黏蛋白的结合情况。
GKN2的差异表达定位于胃的头-尾轴。激光显微切割显示GKN1、GKN2、TFF1 - 3、MUC5AC和MUC6在胃窦腺轴上具有特征性的差异表达谱。GKN2和TFF1均在表层SMCs中表达。令人惊讶的是，TFF1 - GKN2异二聚体不与黏蛋白部分结合；而TFF2仅与黏蛋白结合。
胃窦SMCs的成熟通过表达TFF3的祖细胞的转分化逐步发生。TFF1 - GKN2异二聚体和TFF2在与胃黏蛋白的结合上具有特征性差异。这表明TFF1和TFF2具有不同的生理功能，后者可能作为一种“连接肽”来稳定胃黏液。
