Human coagulation factor X and CD5 antigen-like are potential new members of the zonulin family proteins.

Human coagulation factor X and CD5 antigen-like are potential new members of the zonulin family proteins.
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人凝血因子 X 和 CD5 抗原样是 zonulin 家族蛋白的潜在新成员。

DOI:
10.1016/j.bbrc.2022.11.047
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发表时间:
2023
影响因子:
3.1
通讯作者:
Fasano,Alessio
Fasano,Alessio
中科院分区:
生物学4区
文献类型:
--
作者:
Konno,Takumi;Martinez,EnidE;Ji,Jian;Miranda-Ribera,Alba;Fiorentino,MariaR;Fasano,Alessio

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Zonulin是一种生理性上皮和内皮通透性调节剂。Zonulin增加了抗原从肠腔进入血液和身体各部分之间的运输,这一机制与许多慢性炎症性疾病有关。在它最初被发现时,人们注意到zonulin不是一个单一的蛋白质,而是一个被称为zonulin家族蛋白(ZFPs)的结构和功能相关的蛋白质家族。ZFPs是甘露糖相关丝氨酸蛋白酶(MASP)家族的成员,是导致许多带糖蛋白多态性的高突变率的结果。前珠蛋白2 (Pre-haptoglobin 2)是珠蛋白2的前体,被确定为ZFPs的第一个真核成员,而properdin是替代途径的关键正调节因子,是第二个成员。在这项研究中,我们报告了另外两种可能是ZFPs的蛋白质。人凝血因子X (FX)和CD5抗原样(CD5L)。在Western免疫印迹分析中,FX和CD5L重组蛋白均通过抗zonulin抗体检测到,通过反上皮电阻(TEER)实验证实,这两种蛋白均能降低Caco-2细胞单层的上皮屏障能力。这些结果表明,FX和CD5L与先前鉴定的ZFPs具有结构和功能相似性,因此可以认为是该蛋白家族的新成员。
Zonulin is a physiologic epithelial and endothelial permeability modulator. Zonulin increases antigen trafficking from the gut lumen into the bloodstream and in between body compartments, a mechanism linked to many chronic inflammatory diseases. Upon its initial discovery, it was noted that zonulin was not a single protein, but rather a family of structurally and functionally related proteins referred to as the zonulin family proteins (ZFPs). ZFPs are members of the mannose associated serine proteases (MASP) family and are the result of high mutation rates leading to many zonulin polymorphisms. Pre-haptoglobin 2, the precursor of haptoglobin 2, was identified as the first eukaryotic member of the ZFPs, and properdin, a key positive regulator of the alternative pathway, as a second member. In this study, we report two additional proteins that are likely ZFPs. Human coagulation factor X (FX) and CD5 antigen-like (CD5L). Both FX and CD5L recombinant proteins were detected by anti-zonulin antibody in Western immunoblot analysis, and both proteins decreased epithelial barrier competency of Caco-2 cell monolayers as established by the Trans Epithelial Electrical Resistance (TEER) assay. These results indicate that FX and CD5L have structural and functional similarities with previously identified ZFPs and, therefore, can be considered new members of this family of proteins.
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