Trefoil peptides: from structure to function

Abstract

The unique structure in which six cysteine residues in a sequence of 38 or 39 amino acid residues form three disulphide bonds in a 1-5, 2-4 and 3-6 configuration constitutes the basic elements of a trefoil domain. Today three mammalian trefoil factors (TFF1, TFF2 and TFF3) containing one or two trefoil domains are known. Trefoil factors are usually associated with the mucin layer of the gastrointestinal tract. Early studies on trefoil factors concentrated on structure elucidation and sites of expression in health and disease, whereas studies over the last 3-5 years have focused on the mechanism of action and the search for specific receptors. This review summarises our present knowledge of trefoil peptide structures, their sites of expression, and their protection and repair functions, with a focus on the mechanism by which these peptides exert their biological function.

Intestinal trefoil factor binds to intestinal epithelial cells and induces nitric oxide production: priming and enhancing effects of mucin

“…Nitrite concentration (nmol/ml) DMEM 0.25p0.01 ITF (2.5 µM, 18 h) 0.58p0.03** MucinjITF 1 1.06p0.06** Mucin 2 0.08p0.01…”

“…Their physiological role is not well understood [1]. These peptides contain distinctive cystine-rich ' trefoil ' domains and are resistant to proteolytic degradation [1,2].…”

“…Their physiological role is not well understood [1]. These peptides contain distinctive cystine-rich ' trefoil ' domains and are resistant to proteolytic degradation [1,2]. Three trefoil peptides have been identified in the gastrointestinal tract : pS2 (TFF1), expressed mainly in the stomach [3,4] ; SP (TFF2), in the pancreas and stomach [5] ; and intestinal TFF (ITF or TFF3) in the small and large intestine [6,7].…”

“…Although ITF has been cloned, very little is known about the molecular mechanism of its action [1,16]. A previous investigation has shown that ITF promotes intestinal epithelial migration via a transforming growth factor β-independent pathway [17].…”

Pathophysiological Investigation of the Gastric Surface Mucous Gel Layer of Patients with Helicobacter pylori Infection by Using Immunoassays for Trefoil Factor Family 2 and Gastric Gland Mucous Cell-Type Mucin in Gastric Juice

“…TFFs are mucin-associated peptides containing 1 or 2 characteristic trefoil domains [7]. TFFs along with mucin are involved in mucosal barrier functions and in the healing and repair of mucosal damage as luminal surveillance proteins [8][9][10][11].…”