Gene Expression Profiling in Human Brain Microvascular Endothelial Cells in Response to Treponema pallidum Subspecies pallidum

Wu, Fan; Shen, Kangjie; Xie, Yi; Wang, Hongye; Sun, Yifan; Wang, Qianqiu

doi:10.1590/0001-3765202020191234

Cited by 1 publication

(5 citation statements)

References 42 publications

(22 reference statements)

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“…In our previous study, we observed a significant rise in the ADAMTS5 gene level in HBMEC following treatment with Tp. Additionally, gene ontology enrichment analysis highlighted the involvement of ADAMTS5 in the extracellular region . In the current investigation, both the mRNA and protein levels of ADAMTS5 were significantly elevated after Tp stimulation.…”

Section: Discussionsupporting

confidence: 54%

“…Additionally, gene ontology enrichment analysis highlighted the involvement of ADAMTS5 in the extracellular region. 16 In the current investigation, both the mRNA and protein levels of ADAMTS5 were significantly elevated after Tp stimulation. Moreover, detection of CSF in HIV-negative neurosyphilis patients showed a higher level of ADAMTS5 than that in control.…”

Section: Discussionmentioning

confidence: 45%

“…Our earlier investigation unveiled a significant elevation in the ADAMTS5 mRNA level in primary HBMEC cocultured with Tp. 16 To assess whether a similar increase in ADAMTS5 expression occurred in hCMEC/D3 cells, the cells were exposed to Tp at an MOI of 50:1 for 24 h followed by the detection of ADAMTS5 expression through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), western blot, and immunofluorescence analysis. As depicted in Figure 2A−C, ADAMTS5 expression was significantly elevated compared to the control.…”

Section: Tpmentioning

confidence: 99%

“…In our previous study, we conducted a gene expression profiling analysis on primary HBMEC cocultured with Tp. Our investigation unveiled a significant up-regulation of a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS5) gene . ADAMTS5, a secreted metalloprotease, was known for its capacity to degrade aggrecan .…”

mentioning

confidence: 90%

“…Our investigation unveiled a significant up-regulation of a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS5) gene. 16 ADAMTS5, a secreted metalloprotease, was known for its capacity to degrade aggrecan. 17 Since its discovery in 1999, extensive research had focused primarily on conditions such as osteoarthritis and joint degeneration.…”

mentioning

confidence: 99%

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ADAMTS5 Promotes Permeability of the Blood-Brain Barrier during Treponema pallidum Subspecies pallidum Invading the Central Nervous System

Chen,

Du,

Zhang

et al. 2024

ACS Infect. Dis.

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The pathogenesis of neurosyphilis remains unclear. A previous study found a noteworthy up-regulation of a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS5) gene in human brain microvascular endothelial cells cocultured with Treponema pallidum subspecies pallidum (Tp). To investigate the ADAMTS5 role in Tp invading the central nervous system (CNS), we conducted relevant experiments. Our study revealed that Tp caused an increase in human cortical microvascular endothelial cell/D3 (hCMEC/D3) barrier permeability and significantly enhanced ADAMTS5 expression. The heightened permeability of the hCMEC/D3 barrier was effectively mitigated by inhibiting ADAMTS5. During this process, Tp promoted interleukin-1β production, which, in turn, facilitated ADAMTS5 expression. Furthermore, Tp significantly reduced the glycocalyx on the surface of hCMEC/D3 cells, which was also ameliorated by inhibiting ADAMTS5. Additionally, ADAMTS5 and endothelial glycocalyx components notably increased in the cerebrospinal fluid of HIV-negative neurosyphilis patients. This research provided the first demonstration of the ADAMTS5 role in Tp invading the CNS and offered new insight into neurosyphilis pathogenesis.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 45%

Section: Tpmentioning

confidence: 99%

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confidence: 90%

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confidence: 99%

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