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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
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Protein tyrosine kinase 6 mediates TNFα-induced endothelial barrier dysfunction.
R J Haines1, R S Beard2, M H Wu1
1Department of Surgery, University of South Florida, Morsani College of Medicine, United States.
Biochemical and Biophysical Research Communications
|December 3, 2014
Summary
Protein tyrosine kinase 6 (PTK6) contributes to vascular hyperpermeability by affecting endothelial cell junctions. PTK6 knockdown reduces inflammation-induced barrier dysfunction, revealing a novel role in endothelial barrier regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Systemic inflammation from trauma/shock causes microvascular hyperpermeability and edema.
- The molecular mechanisms of hyperpermeability are not fully understood.
- Protein tyrosine kinase 6 (PTK6) regulates epithelial barriers, but its role in endothelial barriers is unknown.
Purpose of the Study:
- To investigate PTK6 expression in vascular endothelial cells.
- To determine PTK6's role in TNFα-induced endothelial hyperpermeability.
Main Methods:
- Detected PTK6 mRNA and protein in mouse endothelial cells.
- Used electric cell-substrate impedance sensing (ECIS) and transwell albumin-flux assays.
- Performed immunocytochemistry and immunoprecipitation to analyze protein interactions.
Main Results:
- PTK6 is expressed in endothelial cells.
- PTK6 knockdown attenuated TNFα-induced endothelial barrier dysfunction.
- TNFα increased PTK6 association with p120-catenin at cell junctions.
- PTK6 knockdown reduced TNFα-induced VE-cadherin internalization.
Conclusions:
- PTK6 is expressed in vascular endothelial cells.
- PTK6 plays a novel role in mediating endothelial barrier dysfunction.
- PTK6 contributes to TNFα-induced hyperpermeability by affecting VE-cadherin and p120-catenin localization.
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