Related Experiment Video
Updated: Aug 16, 2025
Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Treponema pallidum protein Tp0136 promoting MMPs/TIMPs imbalance via PI3K, MAPK and NF-κB signalling pathways in
Chun-Xiang Cai1,2,3, Shu-Lian Li4, Hui-Ling Lin4
1Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Abstract:
The invasive capability of Treponema. pallidum is central to its infection process. Matrix metalloproteinases (MMPs), which are specifically inhibited by the tissue inhibitors of metalloproteinases (TIMPs), play a pivotal role in promoting pathogenic invasion by destroying tissue barriers within the body. This study aimed to explore the effect of T. pallidum protein Tp0136 on the balance of MMPs/TIMPs in human dermal vascular smooth muscle cells (HDVSMCs) and the related underlying mechanisms. A number of in vitro studies were conducted to access the impact of recombinant Tp0136 protein on the balance of MMPs/TIMPs in HDVSMCs. The involvement of the PI3K, MAPK, and NF-κB signaling pathways in this process was also investigated. Tp0136 induced the mRNA and protein expressions of MMP1 in HDVSMCs in a concentration-dependent way. In addition, MMP1/TIMP1 and MMP1/TIMP2 ratios were also increased. Furthermore, the study demonstrated that treatment of HDVSMCs with Tp0136 activated the PI3K, MAPK, and NF-κB signaling pathways. Inhibition of PI3K, JNK, P38, and NF-κB, suppressed MMP1 expression and reduced the induction of MMP1/TIMP1 and MMP1/TIMP2 ratios by Tp0136. These findings demonstrate that Tp0136 enhanced the expression of MMP1 involving the PI3K, MAPK, and NF-κB signaling pathways in HDVSMCs, and thus generated the unbalance of MMPs/TIMP, which could contribute to the early spread of T. pallidum and pathogenesis of syphilis.
Insights
The Treponema pallidum protein Tp0136 increases matrix metalloproteinase-1 (MMP1) expression in human dermal vascular smooth muscle cells. This imbalance of MMPs/TIMPs, mediated by PI3K/MAPK/NF-κB pathways, may promote syphilis pathogenesis.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Treponema pallidum invasion relies on matrix metalloproteinases (MMPs) that degrade tissue barriers.
- Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity.
- Understanding pathogen-host interactions is crucial for disease pathogenesis.
Purpose of the Study:
- To investigate the effect of T. pallidum protein Tp0136 on MMPs/TIMPs balance in human dermal vascular smooth muscle cells (HDVSMCs).
- To elucidate the underlying molecular mechanisms, including key signaling pathways.
Main Methods:
- In vitro studies using recombinant Tp0136 protein on HDVSMCs.
- Analysis of MMP1, TIMP1, and TIMP2 expression (mRNA and protein).
- Investigation of PI3K, MAPK, and NF-κB signaling pathway activation and inhibition.
Main Results:
- Tp0136 significantly increased MMP1 expression in HDVSMCs in a dose-dependent manner.
- Tp0136 elevated MMP1/TIMP1 and MMP1/TIMP2 ratios.
- Tp0136 activated PI3K, MAPK, and NF-κB signaling pathways, which were essential for MMP1 induction.
Conclusions:
- T. pallidum Tp0136 enhances MMP1 expression via PI3K, MAPK, and NF-κB pathways in HDVSMCs.
- This leads to an imbalance in MMPs/TIMPs, potentially facilitating T. pallidum spread and syphilis pathogenesis.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:20The JAK-STAT Signaling Pathway
01:23Role of Matrix Metalloproteases in Degradation of ECM