Journal
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
Volume 3, Issue 4, Pages 583-597Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsptsci.0c00023
Keywords
trefoil factor family; TFF1; TFF2; TFF3; mucosal protection; gastrointestinal disorders; epithelial wound healing; peptide drug development
Categories
Funding
- European Research Council under the European Union's Horizon 2020 research and innovation program [714366]
- Australian Research Council (ARC) [DE150100784, DP190101667]
- NHMRC Australia [1139366, 1140297, 1156427]
- ARC [DP180101395]
- University of Queensland International Postgraduate Scholarship
- National Health and Medical Research Council of Australia [1156427] Funding Source: NHMRC
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Trefoil factor family peptides (TFF1, TFF2, and TFF3) are key players in protecting, maintaining, and repairing the gastrointestinal tract. Accordingly, they have the therapeutic potential to treat and prevent a variety of gastrointestinal disorders associated with mucosal damage. TFF peptides share a conserved motif, including three disulfide bonds that stabilize a well-defined three-loop-structure reminiscent of a trefoil. Although multiple functions have been described for TFF peptides, their mechanisms at the molecular level remain poorly understood. This review presents the status quo of TFF research relating to gastrointestinal disorders. Putative TFF receptors and protein partners are described and critically evaluated. The therapeutic potential of these peptides in gastrointestinal disorders where altered mucosal biology plays a crucial role in the underlying etiology is discussed. Finally, areas of investigation that require further research are addressed. Thus, this review provides a comprehensive update on TFF literature as well as guidance toward future research to better understand this peptide family and its therapeutic potential for the treatment of gastrointestinal disorders.
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