Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability

The Treponema pallidum membrane protein Tp0136 facilitates Treponema pallidum dissemination, and the permeability of vasculature is intricately linked to the density of the vascular endothelial barrier, which is strongly associated with the morphology of vascular endothelial cells. In this study, ut...

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Main Authors: Yu Lin, Xi Luo, Xu Shen, Xiao‐Lin Fu, Li‐Rong Lin, Tian‐Ci Yang
Format: Article
Language:English
Published: Wiley-VCH 2025-07-01
Series:Small Science
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Online Access:https://doi.org/10.1002/smsc.202500046
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author Yu Lin
Xi Luo
Xu Shen
Xiao‐Lin Fu
Li‐Rong Lin
Tian‐Ci Yang
author_facet Yu Lin
Xi Luo
Xu Shen
Xiao‐Lin Fu
Li‐Rong Lin
Tian‐Ci Yang
author_sort Yu Lin
collection DOAJ
description The Treponema pallidum membrane protein Tp0136 facilitates Treponema pallidum dissemination, and the permeability of vasculature is intricately linked to the density of the vascular endothelial barrier, which is strongly associated with the morphology of vascular endothelial cells. In this study, utilizing the approach of inoculating Tp0136 recombinant protein into the skin lesions of rabbits infected with Treponema pallidum, it was observed that the Tp0136 recombinant protein induced spheroidization of vascular endothelial cells and enlargement of intercellular junctions. By high‐throughput RNA sequencing, the upregulation of the RNA‐binding protein cysteine‐ and glycine‐rich protein 1 (CSRP1) is identified, which modulated the alternative splicing of exon 19 of myosin X (MYO10), which in turn downregulated the expression of MYO10, ultimately inducing morphological spheroidization in vascular endothelial cells. Using CSRP1‐specific shRNA to knock down CSRP1 or using the alternative splicing inhibitor, the spheroidized vascular endothelial cells revert to a flattened state, suggesting that Tp0136 regulates the alternative splicing of MYO10 through CSRP1, leading to a downregulation of MYO10, followed by the spheroidization of vascular endothelial cells and an enlargement of intercellular junctions. These findings contribute to elucidating a mechanism underlying the dissemination of Treponema pallidum.
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spelling doaj-art-bb6e328cb97a4782a8de8d568e0abb662025-08-20T02:36:03ZengWiley-VCHSmall Science2688-40462025-07-0157n/an/a10.1002/smsc.202500046Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular PermeabilityYu Lin0Xi Luo1Xu Shen2Xiao‐Lin Fu3Li‐Rong Lin4Tian‐Ci Yang5Center of Clinical Laboratory School of Medicine Zhongshan Hospital Xiamen University Xiamen University Xiamen Fujian 361000 P. R. ChinaCenter of Clinical Laboratory School of Medicine Zhongshan Hospital Xiamen University Xiamen University Xiamen Fujian 361000 P. R. ChinaInstitute of Infectious Disease School of Medicine Xiamen University Xiamen Fujian 361000 P. R. ChinaCenter of Clinical Laboratory School of Medicine Zhongshan Hospital Xiamen University Xiamen University Xiamen Fujian 361000 P. R. ChinaCenter of Clinical Laboratory School of Medicine Zhongshan Hospital Xiamen University Xiamen University Xiamen Fujian 361000 P. R. ChinaCenter of Clinical Laboratory School of Medicine Zhongshan Hospital Xiamen University Xiamen University Xiamen Fujian 361000 P. R. ChinaThe Treponema pallidum membrane protein Tp0136 facilitates Treponema pallidum dissemination, and the permeability of vasculature is intricately linked to the density of the vascular endothelial barrier, which is strongly associated with the morphology of vascular endothelial cells. In this study, utilizing the approach of inoculating Tp0136 recombinant protein into the skin lesions of rabbits infected with Treponema pallidum, it was observed that the Tp0136 recombinant protein induced spheroidization of vascular endothelial cells and enlargement of intercellular junctions. By high‐throughput RNA sequencing, the upregulation of the RNA‐binding protein cysteine‐ and glycine‐rich protein 1 (CSRP1) is identified, which modulated the alternative splicing of exon 19 of myosin X (MYO10), which in turn downregulated the expression of MYO10, ultimately inducing morphological spheroidization in vascular endothelial cells. Using CSRP1‐specific shRNA to knock down CSRP1 or using the alternative splicing inhibitor, the spheroidized vascular endothelial cells revert to a flattened state, suggesting that Tp0136 regulates the alternative splicing of MYO10 through CSRP1, leading to a downregulation of MYO10, followed by the spheroidization of vascular endothelial cells and an enlargement of intercellular junctions. These findings contribute to elucidating a mechanism underlying the dissemination of Treponema pallidum.https://doi.org/10.1002/smsc.202500046alternative splicingcell spheroidizationpermeabilityTreponema pallidum protein Tp0136vascular endothelial cells
spellingShingle Yu Lin
Xi Luo
Xu Shen
Xiao‐Lin Fu
Li‐Rong Lin
Tian‐Ci Yang
Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability
Small Science
alternative splicing
cell spheroidization
permeability
Treponema pallidum protein Tp0136
vascular endothelial cells
title Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability
title_full Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability
title_fullStr Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability
title_full_unstemmed Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability
title_short Treponema pallidum Protein Tp0136 Induces Spheroidization of Vascular Endothelial Cells, Resulting in Widened Intercellular Junctions and Enhanced Vascular Permeability
title_sort treponema pallidum protein tp0136 induces spheroidization of vascular endothelial cells resulting in widened intercellular junctions and enhanced vascular permeability
topic alternative splicing
cell spheroidization
permeability
Treponema pallidum protein Tp0136
vascular endothelial cells
url https://doi.org/10.1002/smsc.202500046
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