Keratinocyte growth factor promotes goblet cell differentiation through regulation of goblet cell silencer inhibitor

dBackground & Aims: Keratinocyte growth factor (KGF) is an epithelial cell- specific growth factor. Previous reports demonstrated that HGF induces diff erentiation of epithelial cells of gastrointestinal tract in vivo, especial ly goblet cell-specific lineage stimulation. Intestinal trefoil factor (ITF ) is selectively expressed in intestinal goblet cells and its expression co rrelates with intestinal goblet cell differentiation. In this study, we ana lyzed the mechanism of HGF modulation of goblet cell differentiation throug h characterization of its effects on ITF gene expression. Methods: Subclone H2 of the human colonic epithelial cell line HT-29, which can be induced t o intestinal goblet cells, was treated with KGF and characterized by Northe rn and Western blot analyses, transient transfection assays, and electropho retic mobility shift assays (EMSAs). Results: KGF promoted differentiation of H2 cells to goblet cells as reflected by induced ITF expression, Transie nt transfection assays revealed that HGF regulates mouse ITF transcription through the goblet cell silencer inhibitor (GCSI) element, which is essenti al for goblet cell-specific expression of ITF. EMSAs showed that KGF induce s GCSI binding protein (GCSI-BP). Conclusions: HGF promotes goblet cell dif ferentiation through the induction of GCSI-BP, a goblet cell-specific trans cription factor. GCSI-BP may play a central role in intestinal goblet cell differentiation.