摘要
粘液上皮受到复杂的粘液屏障层的保护,这是先天免疫防御的一部分。三叶因子家族肽 TFF1、TFF2 和 TFF3 具有凝集素活性,主要与来自这些上皮的粘蛋白共同分泌。 TFF1 和 TFF2 主要在胃黏膜中表达,而 TFF3 从大多数黏液上皮及其腺体中广泛分泌。 TFF1 和 TFF3 由单个 TFF 结构域和一个额外的游离第 7 个半胱氨酸残基组成,而 TFF2 包含两个 TFF 结构域。对 TFFs 分子形式的系统分析为其不同的分子功能提供了新的见解。 TFF1 主要作为具有不寻常的游离硫醇基团的单体存在,只有少量形成二硫键连接的同二聚体以及与 gastrokine-2 和 IgG-Fc 结合蛋白 (FCGBP) 的异二聚体。 TFF3 主要在体内与 FCGBP 形成异二聚体,但在体外也与恶性脑肿瘤/gp340 (DMBT1gp340) 中的缺失结合。相比之下,TFF2 作为凝集素与粘蛋白 MUC6 的保守 O 连接碳水化合物部分结合。 FCGBP 和 DMBT1gp340 均由大多数黏液上皮及其腺体分泌,并参与黏膜先天免疫。因此,出现了一张新图,指出 TFF3-FCGBP(和 TFF1-FCGBP)对粘膜先天免疫防御的功能,例如。支持清除微生物。 DMBT1gp340 可以很好地支持这样的功能。相比之下,TFF2/MUC6 凝集素复合物可能在物理上稳定内部粘附的胃粘液层。此外,有迹象表明 TFF3-FCGBP 也可能在血管中发挥作用。
关键词: 先天免疫、炎症、三叶因子、凝集素、粘蛋白、FCGBP、DMBT1、SARS-CoV-2。
Current Medicinal Chemistry
Title:Trefoil Factor Family (TFF) Peptides and their Different Roles in the Mucosal Innate Immune Defense and More: An Update
Volume: 28 Issue: 36
关键词: 先天免疫、炎症、三叶因子、凝集素、粘蛋白、FCGBP、DMBT1、SARS-CoV-2。
摘要: Mucous epithelia are protected by complex mucus barrier layers, which are part of the innate immune defense. Trefoil factor family peptides TFF1, TFF2, and TFF3 have lectin activities and are predominantly co-secreted together with mucins from these epithelia. TFF1 and TFF2 are mainly expressed in the gastric mucosa, whereas TFF3 is widely secreted from most mucous epithelia and their glands. TFF1 and TFF3 consist of a single TFF domain and an additional free 7th cysteine residue, whereas TFF2 contains two TFF domains. Systematic analyses of the molecular forms of TFFs gave new insights into their diverse molecular functions. TFF1 mainly exists as a monomer with an unusual free thiol group and only minor amounts form a disulfide-linked homodimer as well as heterodimers with gastrokine-2 and IgG-Fc-binding protein (FCGBP). TFF3 mainly forms a heterodimer with FCGBP in vivo, but also binds Deleted in Malignant Brain Tumors/gp340 (DMBT1gp340) in vitro. In contrast, TFF2 binds as a lectin to a conserved O-linked carbohydrate moiety of the mucin MUC6. Both FCGBP and DMBT1gp340 are secreted by most mucous epithelia and their glands and are involved in mucosal innate immunity. Thus, a new picture emerged pointing to functions of TFF3-FCGBP (and TFF1-FCGBP) for mucosal innate immune defense, e.g. supporting the clearing of the microorganisms. Such a function could be well be supported by DMBT1gp340. In contrast, the TFF2/MUC6 lectin complex probably physically stabilizes the inner adherent gastric mucus layer. Furthermore, there are indications that TFF3- FCGBP might also play a role in the blood vessels.
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Trefoil Factor Family (TFF) Peptides and their Different Roles in the Mucosal Innate Immune Defense and More: An Update, Current Medicinal Chemistry 2021; 28 (36) . https://dx.doi.org/10.2174/0929867328666210215114140
DOI https://dx.doi.org/10.2174/0929867328666210215114140 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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