Recombinant <i>Treponema pallidum</i> protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells

Gao, Zhengxiang; Luo, Xi; Liu, L.‐L.; Lin, Li‐Rong; Tong, Man‐Li; Yang, Tian‐Ci

doi:10.1111/jdv.15725

Cited by 19 publications

(32 citation statements)

References 33 publications

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“…Treponema pallidum affects endothelial cells the present study also provides evidence that TP47 causes an imbalance of matrix metalloproteinase (MMP)/tissue inhibitors of matrix metalloproteinase (TIMP) by increasing the expression and activity of MMP-1 and MMP-10 and prompts angiogenesis through Akt/mTOR/S6 signaling in HUVECs 25. Tp0435/Tp17 can regulate the expression of ve-cadherin (cadherin) membrane and F-actin rearrangement of human vascular endothelial cells, change the connection between endothelial cells, and improve the permeability of vascular endothelial barrier 26.…”

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confidence: 61%

Possible effects of Treponema pallidum infection on human vascular endothelial cells

Xie

Zhao

et al. 2022

Clinical Laboratory Analysis

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Treponema pallidum belongs to the Spirochaetaceae (spirochetes), ranging from 6 to 15 µm in length, with a diameter of 0.2 µm. It can cause syphilis, a sexually transmitted disease with multiple stages and development that seriously endangers human health, causing 6.3 million new infections each year. 1 Treponema pallidum directly across the mucous membranes of the host or broken skin caused by sexual activity. From a series of previous bioinformatics analyses related to genomics of T. pallidum, it can be seen that T. pallidum lacks a complete biosynthetic pathway, 2,3 which may not satisfy its own needs for survival in the host, so T. pallidum obtains important or essential macromolecules during the infection of host cells. At the same time, the barrier function of the vascular endothelium of the host is destroyed, allowing it to enter the blood and then spread to the distal tissues and organs through flow of blood. 4 Therefore, T. pallidum attaching to and altering host cells (such as endothelial cells) and extracellular matrix are a key initial steps for infection.Treponema pallidum bind to vascular endothelial receptors (unfortunately, the specific receptors are still unknown) by the bacteria adhesion protein (adhesins such as Tp0751, Tp0136, and Tp0155.) (Table 1) to penetrate tissue barriers, such as the intima of vascular endothelium. [5][6][7] It has also been determined that TP0326/Tp92 is a T. pallidum outer membrane protein, and it is presumed that Tp92 also helps T. pallidum attach to host endothelial cells according to the function of homologous protein for mediating cell adhesion. 8 Treponema pallidum then spreads throughout the whole body utilizing blood circulation through tissue and vascular endothelial barriers (e.g., blood-brain barrier and placental barrier), causing multiple organ and tissue infections. 9 However, it

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confidence: 61%

Possible effects of Treponema pallidum infection on human vascular endothelial cells

Xie

Zhao

et al. 2022

Clinical Laboratory Analysis

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“…The period for the lesions to appear may vary between 10 and 90 days 4,5,7 . Microscopically, it is characterized by a proliferation of blood vessels surrounded by lymphocytes, macrophages and plasma cells 10,11 . In hematoxylin and eosin (HE) staining, the epithelial surface is ulcerated, with the presence of intense chronic inflammatory infiltrate predominantly of lymphocytes and plasma cells, generally with perivascular pattern 12 .…”

Section: Introductionmentioning

confidence: 99%

“…Because of these varied clinical manifestations , syphilis has been known as "the great imitator" [2][3][4] . Microscopically, an inflammatory infiltrate containing monocytes recruited from the peripheral circulation and increased angiogenesis is observed 10,11 . The surface may be ulcerated or hyperplastic with spongiosis and exocytosis, associated with a deep and dense underlying plasmocytic inflammatory infiltrate 12 .…”

Section: Introductionmentioning

confidence: 99%

Syphilis Diagnosis through Oral Lesions of Different Clinical Aspects: Report of 3 Cases

et al. 2021

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Syphilis is a sexually transmitted infection, caused by the anaerobic spirochete Treponema pallidum. It is characterized by a variety of clinical manifestations including the oral mucosa, mimicking several diseases, thereby making diagnosis a challenge for clinicians. Therefore, the objective of this work is to report three cases of syphilis that were diagnosed based on oral lesions of different clinical aspects. In this series of cases, the lesions were found on the tongue and hard palate and presented as white plaques, ulcers or erythematous spots associated with ulcers. In the two cases, incisional biopsy was performed, and the histopathological aspects were suggestive of syphilis. Treponemic and non-treponemic tests were positive for all the patients, confirming syphilis. Therapy with benzathine-penicillin, administered intramuscularly led to complete remission of oral lesions in all the patients. The syphilis reemergence in the last years demands its inclusion in the differential diagnosis of several oral lesions. Diagnosing syphilis by oral lesions can be difficult once it can mimic other conditions. Therefore, dentists should know the clinical aspects of this infection, since many cases may exhibit only oral manifestations, to help in the diagnosis and control of the infection spread. Keywords: Syphilis. Treponemal Infections. Oral Manifestations. ResumoA sífilis é uma infecção sexualmente transmissível, causada pela espiroqueta anaeróbia Treponema pallidum. É caracterizada por uma variedade de manifestações clínicas, incluindo a mucosa oral, podendo mimetizar várias doenças, tornando o diagnóstico um desafio. Portanto, o objetivo deste trabalho é relatar três casos de sífilis diagnosticados a partir de lesões orais de diferentes aspectos clínicos. Nesta série de casos, as lesões foram encontradas na língua e palato duro e apresentadas como placas brancas, úlceras ou manchas eritematosas associadas a úlceras. Em dois casos, foi realizada biópsia incisional e os aspectos histopatológicos foram sugestivos de sífilis. Os testes treponêmicos e não treponêmicos foram positivos para todos os pacientes, confirmando a sífilis. A terapia com penicilina benzatina, administrada por via intramuscular, levou à remissão completa das lesões orais em todos os pacientes. O ressurgimento da sífilis nos últimos anos exige sua inclusão no diagnóstico diferencial de várias lesões bucais. O diagnóstico da sífilis por lesões orais pode ser difícil, pois pode mimetizar outras condições. Portanto, o dentista deve conhecer os aspectos clínicos dessa infecção, pois muitos casos podem apresentar apenas manifestações orais, para auxiliar no diagnóstico e controle da disseminação da infecção. Palavras-chave: Sífilis. Infecção Treponêmica. Manifestações Orais.

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“…As a common sexually transmitted disease, syphilis has been a threat to human health for centuries . According to its clinical characterization, syphilis can be divided into three stages: primary syphilis, secondary syphilis and tertiary syphilis.…”

Section: Introductionmentioning

confidence: 99%

“…As a common sexually transmitted disease, syphilis has been a threat to human health for centuries. 1,2 According to its clinical characterization, syphilis can be divided into three stages: primary syphilis, secondary syphilis and tertiary syphilis. The main characteristic of primary syphilis is that the skin infection site has a typical chancre, a painless ulceration.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Treponema pallidum protein Tp0136 promotes fibroblast migration by modulating MCP‐1/CCR2 through TLR4

Luo

Gao

Lin

et al. 2020

Acad Dermatol Venereol

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Background Chancre self‐healing is an important clinical feature in the early stages of syphilis infection. Wound healing may involve an important mechanism by the migration of fibroblasts filling the injured lesion. However, the specific mechanism underlying this process is still unknown. Objectives We aimed to analyse the role of Tp0136 in the migration of fibroblasts and the related mechanism. Methods The migration ability of fibroblasts was detected by a wound‐healing assay. RT‐PCR and ELISA detected the expression of MCP‐1, IL‐6 and MMP‐9. TLR4 expression was detected by RT‐PCR. The protein levels of CCR2 and relevant signalling pathway molecules were measured by Western blotting. Results Tp0136 significantly promoted fibroblast migration. Subsequently, the levels of MCP‐1 and its receptor CCR2 were increased in this process. The migration of fibroblasts was significantly inhibited by an anti‐MCP‐1 neutralizing antibody or CCR2 inhibitors. Furthermore, studies demonstrated that Tp0136 could activate the ERK/JNK/PI3K/NF‐κB signalling pathways through TLR4 activity and that signalling pathways inhibitors could weaken MCP‐1 secretion and fibroblast migration. Conclusions These findings demonstrate that Tp0136 promotes the migration of fibroblasts by inducing MCP‐1/CCR2 expression through signalling involving the TLR4, ERK, JNK, PI3K and NF‐κB signalling pathways, which could contribute to the mechanism of chancre self‐healing in syphilis.

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Recombinant Treponema pallidum protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells

Cited by 19 publications

References 33 publications

Possible effects of Treponema pallidum infection on human vascular endothelial cells

Possible effects of Treponema pallidum infection on human vascular endothelial cells

Syphilis Diagnosis through Oral Lesions of Different Clinical Aspects: Report of 3 Cases

Recombinant Treponema pallidum protein Tp0136 promotes fibroblast migration by modulating MCP‐1/CCR2 through TLR4

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