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

doi:10.1021/acsptsci.0c00023

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

ACS Pharmacol Transl Sci. 2020 Jun 9;3(4):583-597. doi: 10.1021/acsptsci.0c00023. eCollection 2020 Aug 14.

Authors

Nayara Braga Emidio¹, Stuart M Brierley^{2

3

4}, Christina I Schroeder^{1

5}, Markus Muttenthaler^{6

1}

Affiliations

¹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
² Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medicial Research Insittitue (FHMRI), Flinders University, Bedford Park, South Australia 5042, Australia.
³ Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia 5000, Australia.
⁴ Discipline of Medicine, University of Adelaide, Adelaide, South Australia 5000, Australia.
⁵ National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.
⁶ Institute of Biological Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.

Abstract

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.

Publication types

Review