Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
Int J Mol Sci. 2020 Jun 25;21(12):4535. doi: 10.3390/ijms21124535.
Trefoil factor family peptides (TFF1, TFF2, TFF3) are typically co-secreted together with mucins. represents a gastric tumor suppressor gene in mice. TFFs are also synthesized in minute amounts in the immune and central nervous systems. In mucous epithelia, they support rapid repair by enhancing cell migration ("restitution") via their weak chemotactic and anti-apoptotic effects. For a long time, as a paradigm, this was considered as their major biological function. Within recent years, the formation of disulfide-linked heterodimers was documented for TFF1 and TFF3, e.g., with gastrokine-2 and IgG Fc binding protein (FCGBP). Furthermore, lectin activities were recognized as enabling binding to a lipopolysaccharide of (TFF1, TFF3) or to a carbohydrate moiety of the mucin MUC6 (TFF2). Only recently, gastric TFF1 was demonstrated to occur predominantly in monomeric forms with an unusual free thiol group. Thus, a new picture emerged, pointing to diverse molecular functions for TFFs. Monomeric TFF1 might protect the gastric mucosa as a scavenger for extracellular reactive oxygen/nitrogen species. Whereas, the TFF2/MUC6 complex stabilizes the inner layer of the gastric mucus. In contrast, the TFF3-FCGBP heterodimer (and also TFF1-FCGBP) are likely part of the innate immune defense of mucous epithelia, preventing the infiltration of microorganisms.
三叶因子家族肽（TFF1、TFF2、TFF3）通常与黏蛋白一起共同分泌。TFF1 基因在小鼠中是胃肿瘤的抑制基因。TFFs 也以微量的形式在免疫系统和中枢神经系统中合成。在黏液上皮中，它们通过弱趋化作用和抗细胞凋亡作用促进细胞迁移（“修复”）来支持快速修复。长期以来，这一直被视为它们的主要生物学功能。近年来，已经记录了 TFF1 和 TFF3 与 gastrokine-2 和 IgG Fc 结合蛋白（FCGBP）形成二硫键连接的异源二聚体。此外，还发现了凝集素活性，使其能够与 TFF1、TFF3 的脂多糖（TFF1、TFF3）或黏蛋白 MUC6 的碳水化合物部分（TFF2）结合。直到最近，才证明胃 TFF1 主要以单体形式存在，并具有异常的游离巯基。因此，出现了一个新的画面，指出 TFFs 具有多种分子功能。单体 TFF1 可能作为细胞外活性氧/氮物种的清除剂来保护胃黏膜。相比之下，TFF2/MUC6 复合物稳定胃黏液的内层。相反，TFF3-FCGBP 异源二聚体（以及 TFF1-FCGBP）可能是黏液上皮固有免疫防御的一部分，可防止微生物的渗透。
