Trefoil factor 3 (TFF3)

Trefoil factor 3 (TFF3) is a small, highly stable secreted peptide (about 59 amino acids, 7–9 kDa) characterized by a conserved trefoil domain with multiple disulfide bonds[1][2]. It is predominantly produced by goblet cells in the gastrointestinal tract, and co-secreted with mucins to maintain epithelial integrity, reduce permeability, stimulate migration and restitution after injury, and suppress inflammation[1][4][6]. TFF3 achieves these effects partly through binding mucins and specific receptors—CXCR4, CXCR7, and PAR-2—activating key signaling pathways for cell migration, wound healing, and immune defense[3][2][1]. While essential for mucosal homeostasis, TFF3 is increasingly implicated in cancer progression, poor prognosis, metabolic disorders, and emerging roles in neuroendocrine regulation[3][5][1].

Other names

TFF3ITFP1BTFIintestinal trefoil factor

Mucosal protection and restitution via interaction with mucins and enhancement of barrier function; Activation of cell migration and healing via binding to CXCR4, CXCR7, PAR-2, and LINGO2-EGFR signaling complexes; Suppression and modulation of inflammatory pathways (e.g., MAPK, NF-κB, STAT3, PI3K, mTOR, HIF-1α)