2. Academic Validation
  3. Tp0136 targets fibronectin (RGD)/Integrin β1 interactions promoting human microvascular endothelial cell migration

Tp0136 targets fibronectin (RGD)/Integrin β1 interactions promoting human microvascular endothelial cell migration

  • Exp Cell Res. 2020 Nov 1;396(1):112289. doi: 10.1016/j.yexcr.2020.112289.
Xi Luo 1,  Shu-Wen Lin 2,  Qiu-Yan Xu 1,  Wu-Jian Ke 3,  Zheng-Xiang Gao 1,  Man-Li Tong 4,  Li-Li Liu 4,  Li-Rong Lin 4,  Hui-Lin Zhang 5,  Tian-Ci Yang 6
Affiliations

Affiliations

  • 1 Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China.
  • 2 Clinical Laboratory, Xiamen Children's Hospital, Children's Hospital of Fudan University Xiamen Branch, Xiamen, 361006, China.
  • 3 Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China.
  • 4 Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China.
  • 5 Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China. Electronic address: [email protected].
  • 6 Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China. Electronic address: [email protected].
PMID: 32950474 DOI: 10.1016/j.yexcr.2020.112289
Abstract

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.

Keywords

CCL2; Fibronectin; Integrin β1; Migration; RGD; Tp0136.

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