Biosynthesis of Gastrokine-2 in the Human Gastric Mucosa: Restricted Spatial Expression along the Antral Gland Axis and Differential Interaction with TFF1, TFF2 and Mucins

Abstract

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. Methods: 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. Results: 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. Conclusions: 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.