Multiple regulatory pathways for trefoil factor (TFF) genes.

The expression of trefoil peptides and their biological consequences are regulated in a multifactorial fashion, and much more work is required in order to fully understand the underlying molecular mechanisms. Central to this will be the identification and functional analysis of trefoil peptide receptors and the full complement of binding proteins. This review summarizes the often fragmentary information available on the environmental, chemical and local regulatory molecules that control trefoil gene expression. Special attention is paid to the nature of the signaling cascades that are activated and the binding proteins that modulate gene transcription. Epigenetic regulation of trefoil gene expression, particularly the role of (de)methylation is described, and the signaling pathways downstream of trefoil peptide activation of target cells are enumerated, as are their physiological and pathological outcomes.