Lesion healing without treatment is a unique clinical characteristic of the early stages of syphilis infection. Angiogenesis, which involves endothelial cell migration, is an important process in wound healing. Tp0136, an outer membrane protein of T. pallidum, has the ability to bind host fibronectin-producing cells, which plays a crucial role in the pathogenesis of syphilis. In this research, we purposed to analyze the role of Tp0136 in the migration of human microvascular endothelial (HMEC-1) cells and to explore the related mechanism. First, Tp0136 significantly promoted HMEC-1 cell migration. Furthermore, the levels of C–C motif ligand 2 (CCL2) mRNA and protein expression rose with the concentration and time increasing of Tp0136. The migration of HMEC-1 cells was significantly suppressed by an anti-CCL2 antibody and a CCR2 (the CCL2 receptor) inhibitor. Further study revealed that, in cells pretreated with anti-fibronectin antibody, anti-integrin β1 antibody or RGD (Arg-Gly-Asp), the expression levels of CCL2 induced by Tp0136 were notably decreased. Additionally, after pretreatment with an anti-fibronectin antibody, an anti-integrin β1 antibody or RGD, the migration of HMEC-1 cells treated with Tp0136 was obviously suppressed. These results show that Tp0136 promots the migration of HMEC-1 cells by inducing CCL2 expression via the interaction of the fibronectin RGD domain with integrin β1 and the CCL2/CCR2 signaling pathway, and these interactions may contribute to the mechanisms that increase the capacity for self-healing syphilis infection.

未经治疗的病灶愈合是梅毒感染早期的独特临床特征。涉及内皮细胞迁移的血管生成是伤口愈合的重要过程。Tp0136，苍白螺旋体的外膜蛋白具有结合宿主产生纤连蛋白的细胞的能力，这在梅毒的发病机理中起着至关重要的作用。在这项研究中，我们旨在分析Tp0136在人类微血管内皮（HMEC-1）细胞迁移中的作用，并探讨相关机制。首先，Tp0136显着促进HMEC-1细胞迁移。此外，CC主题配体2（CCL2）mRNA和蛋白质表达水平随Tp0136浓度和时间的增加而增加。HMEC-1细胞的迁移被抗CCL2抗体和CCR2（CCL2受体）抑制剂显着抑制。进一步的研究表明，在用抗纤连蛋白抗体，抗整合素β1抗体或RGD（Arg-Gly-Asp）预处理的细胞中，Tp0136诱导的CCL2的表达水平显着降低。另外，用抗纤连蛋白抗体，抗整合素β1抗体或RGD预处理后，用Tp0136处理的HMEC-1细胞的迁移明显受到抑制。这些结果表明，Tp0136通过纤连蛋白RGD结构域与整合素β1和CCL2 / CCR2信号通路的相互作用诱导CCL2表达，从而促进HMEC-1细胞的迁移，并且这些相互作用可能有助于增加自身能力的机制。治愈梅毒感染。