The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigration Article Swipe
Alex L. Wilkinson
,
Samuel Hulme
,
James I. Kennedy
,
Emily R. Mann
,
Paul Horn
,
Emma L. Shepherd
,
Kelvin Yin
,
Marco Y. W. Zaki
,
Gareth Hardisty
,
Wei‐Yu Lu
,
Pia Rantakari
,
David H. Adams
,
Marko Salmi
,
Matthew Hoare
,
Daniel A. Patten
,
Shishir Shetty
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1016/j.isci.2023.107966
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1016/j.isci.2023.107966
Liver sinusoidal endothelial cells (LSEC) undergo significant phenotypic change in chronic liver disease (CLD), and yet the factors that drive this process and the impact on their function as a vascular barrier and gatekeeper for immune cell recruitment are poorly understood. Plasmalemma-vesicle-associated protein (PLVAP) has been characterized as a marker of LSEC in CLD; notably we found that PLVAP upregulation strongly correlated with markers of tissue senescence. Furthermore, exposure of human LSEC to the senescence-associated secretory phenotype (SASP) led to a significant upregulation of PLVAP. Flow-based assays demonstrated that SASP-driven leukocyte recruitment was characterized by paracellular transmigration of monocytes while the majority of lymphocytes migrated transcellularly. Knockdown studies confirmed that PLVAP selectively supported monocyte transmigration mediated through PLVAP's impact on LSEC permeability by regulating phospho-VE-cadherin expression and endothelial gap formation. PLVAP may therefore represent an endothelial target that selectively shapes the senescence-mediated immune microenvironment in liver disease.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.isci.2023.107966
- OA Status
- gold
- Cited By
- 4
- References
- 65
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386859161
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4386859161Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.isci.2023.107966Digital Object Identifier
- Title
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The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigrationWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-09-19Full publication date if available
- Authors
-
Alex L. Wilkinson, Samuel Hulme, James I. Kennedy, Emily R. Mann, Paul Horn, Emma L. Shepherd, Kelvin Yin, Marco Y. W. Zaki, Gareth Hardisty, Wei‐Yu Lu, Pia Rantakari, David H. Adams, Marko Salmi, Matthew Hoare, Daniel A. Patten, Shishir ShettyList of authors in order
- Landing page
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https://doi.org/10.1016/j.isci.2023.107966Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1016/j.isci.2023.107966Direct OA link when available
- Concepts
-
Downregulation and upregulation, Cell biology, Senescence, Biology, Immune system, Monocyte, Endothelial stem cell, Immunology, In vitro, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 3Per-year citation counts (last 5 years)
- References (count)
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65Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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