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Recombinant Treponema pallidum protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells.
J Eur Acad Dermatol Venereol. 2019 Oct; 33(10):1958-1970.JE

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.

Authors+Show Affiliations

Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China. Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China. Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China. Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China. Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31166625

Citation

Gao, Z-X, et al. "Recombinant Treponema Pallidum Protein Tp47 Induces Angiogenesis By Modulating the Matrix Metalloproteinase/tissue Inhibitor of Metalloproteinase Balance in Endothelial Cells." Journal of the European Academy of Dermatology and Venereology : JEADV, vol. 33, no. 10, 2019, pp. 1958-1970.
Gao ZX, Luo X, Liu LL, et al. Recombinant Treponema pallidum protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells. J Eur Acad Dermatol Venereol. 2019;33(10):1958-1970.
Gao, Z. X., Luo, X., Liu, L. L., Lin, L. R., Tong, M. L., & Yang, T. C. (2019). Recombinant Treponema pallidum protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells. Journal of the European Academy of Dermatology and Venereology : JEADV, 33(10), 1958-1970. https://doi.org/10.1111/jdv.15725
Gao ZX, et al. Recombinant Treponema Pallidum Protein Tp47 Induces Angiogenesis By Modulating the Matrix Metalloproteinase/tissue Inhibitor of Metalloproteinase Balance in Endothelial Cells. J Eur Acad Dermatol Venereol. 2019;33(10):1958-1970. PubMed PMID: 31166625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant Treponema pallidum protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells. AU - Gao,Z-X, AU - Luo,X, AU - Liu,L-L, AU - Lin,L-R, AU - Tong,M-L, AU - Yang,T-C, Y1 - 2019/07/10/ PY - 2019/01/28/received PY - 2019/05/08/accepted PY - 2019/6/6/pubmed PY - 2020/3/12/medline PY - 2019/6/6/entrez SP - 1958 EP - 1970 JF - Journal of the European Academy of Dermatology and Venereology : JEADV JO - J Eur Acad Dermatol Venereol VL - 33 IS - 10 N2 - 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. SN - 1468-3083 UR - https://www.unboundmedicine.com/medline/citation/31166625/Recombinant_Treponema_pallidum_protein_Tp47_induces_angiogenesis_by_modulating_the_matrix_metalloproteinase/tissue_inhibitor_of_metalloproteinase_balance_in_endothelial_cells_ L2 - https://doi.org/10.1111/jdv.15725 DB - PRIME DP - Unbound Medicine ER -