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Δευτέρα 10 Ιουνίου 2019

Recombinant Treponema pallidum proteinTp47 induces angiogenesis by modulating the MMP/TIMP balance in endothelial cells
Zheng‐Xiang Gao  Xi Luo  Li‐Li Liu  Li‐Rong Lin  Man‐Li Tong  Tian‐Ci Yang
First published: 05 June 2019 https://doi.org/10.1111/jdv.15725
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jdv.15725
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Abstract
Background
Although angiogenesis is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the underlying mechanisms of angiogenesis induced by reactions to Treponema pallidum antigens.

Objective
In this study, we sought to determine the role of recombinant T. pallidum Tp47 in promoting angiogenesis in endothelial cells and the related mechanism.

Methods
Evaluation of the pro‐angiogenic activity of recombinant T. pallidum Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed, and the balance of matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) and the mechanisms underlying the involvement of Akt/mTOR/S6 pathways in this process were explored.

Results
Under stimulation by Tp47, HUVECs exhibited obvious proliferation, migration and tube formation. In addition, the apparent promotion of angiogenesis by Tp47 was observed using a zebrafish embryo model. During angiogenesis, the levels of MMP‐1 and MMP‐10 were significantly elevated, whereas those of TIMP‐1 and TIMP‐2 did not change. In addition, after transfection with siRNAMMP‐1 and siRNAMMP‐10, migration and tube formation were significantly inhibited. Akt/mTOR/S6 signalling was found to be involved in upregulating MMP‐1 and MMP‐10 expression, and the sequential blockade of steps in the pathways effectively prevented Tp47‐induced angiogenesis.

Conclusion
The results reveal the underlying mechanism of angiogenesis promoted by Tp47, namely, upregulating MMP‐1 and MMP‐10 expression to disrupt the MMP/TIMP balance through the Akt/mTOR/S6 pathway. These findings contribute to our understanding of the pathophysiology of syphilis.

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