Diverse Functions of Bioactive Peptide Trefoil Factor 3: from Laboratory to Clinic

Trefoil factor 3 (TFF3) is the last small molecule peptide found in the trefoil factor family. It is mainly secreted by intestinal goblet cells and exerts mucosal repair effect in gastrointestinal tract. Emerging evidence indicated that TFF3 is not only expressed in intestinal tract, but also in female reproductive, urinary, respiratory, immune, nervous and endocrine system. Although TFF3 is widely distributed in human healthy samples, its specific physiological significance is unclear. This review provides an up-to-date overview of the biological functions of TFF3 and summarizes its expression sites, binding proteins, signaling pathways and clinical applications. We found that TFF3 mediated signaling pathways mainly include MAPK, NF-κB, PI3K, STAT3 and HIF-1. More importantly, mucosal protection would no longer be the only application of TFF3. As TFF3 gradually exhibits the potential for immune regulation, neuroprotection, and regulation of glycolipid metabolism, it may get many interesting clinical applications in the future.