Structure, Function, and Therapeutic Potential of the Trefoil Factor Family in the Gastrointestinal Tract

Nayara Braga Emidio, Stuart M. Brierley, Christina I. Schroeder, Markus Muttenthaler

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)583-597
Number of pages15
JournalACS Pharmacology and Translational Science
Issue number4
Publication statusPublished - 14 Aug 2020


  • epithelial wound healing
  • gastrointestinal disorders
  • mucosal protection
  • peptide drug development
  • TFF1
  • TFF2
  • TFF3
  • trefoil factor family


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