Trefoil factors — new markers of gastrointestinal mucosal barrier

Abstract

Trefoil factors (TFFs) are peptides containing a cloverleaf-like structure, which are synthesized in diverse organs including various regions of the human brain (presumably involved in nervous system development and differentiation), thyroid gland, mammary gland, uterus, prostate gland, conjunctiva, respiratory tract, salivary glands, and gall bladder, which peaks in diverse gastrointestinal tract mucosa: TFF-1 in the stomach, TFF-2 in the stomach and duodenum, and TFF-3 in the gut. An increasing body of studies indicate not only about a widely distributed trefoil factors in vivo but also points at their important regulatory functions. In particular, TFFs affect cell adhesion by enhancing epithelial cell migration. Recovery of reversibly damaged epithelial structures called restitution is also facilitated due to TFF-related antiapoptotic effect (anoikis resistance). In contrast, TFF-mediated proangiogenic effects can promote tumor angiogenesis, whereas their immunomodulatory effects include an influence on expression of pro-inflammatory and defense factors (including nitric oxide, cytokines, and defensins). Moreover, TFFs interacting with mucin may increase mucus viscosity, thereby protecting the mucosal layers against ulcerogenic agents. However, bronchial asthma maybe aggravated by elevating mucus viscosity in the respiratory tract due to TFF-2. In addition, TFF expression level is associated with pathogenesis of inflammatory diseases in the gastrointestinal tract. It was shown that modality of changes in TFF level might differ depending on anatomical location and severity of lesions. Changing TFF level plays an important role in oncogenesis. For instance, gastric and colorectal cancer is accompanied by upregulated TFF-1 expression. Importantly, TFF amount is considered as a diagnostic predictor due to being associated with carcinogenesis stage, metastasis as well as sensitivity to chemotherapy in gastrointestinal cancer. In addition, a role potentially played by TFFs in other malignancies including retinoblastoma, breast cancer, and thyroid carcinoma has been extensively examined. Thus, an expanding range of experimental and clinical data evidence that trefoil factors maybe considered as a promising marker of gastrointestinal and oncology diseases.