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T-cadherin modulates endothelial barrier function
Alexandra V Andreeva1, Jingyan Han, Mikhail A Kutuzov
1Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. aandreev@uic.edu
Journal of Cellular Physiology
|December 30, 2009
Summary
T-cadherin depletion modestly reduced endothelial barrier resistance and altered signaling pathways. This atypical cadherin plays a role in endothelial barrier function and thrombin response.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- T-cadherin is an atypical cadherin lacking transmembrane and intracellular domains, anchored to the plasma membrane via glycosylphosphatidylinositol.
- Unlike canonical cadherins, T-cadherin is primarily considered a signaling molecule and is highly expressed in endothelial cells.
Purpose of the Study:
- To investigate the role of T-cadherin in regulating endothelial barrier function.
- To elucidate the signaling pathways influenced by T-cadherin in endothelial cells.
Main Methods:
- Transendothelial electrical resistance (TEER) measurements in human umbilical vein endothelial cells (HUVECs).
- siRNA-mediated depletion of T-cadherin.
- Analysis of protein phosphorylation (Akt, LIM kinase, p38 MAP kinase, cofilin) and tubulin acetylation.
- Assessment of responses to serum stimulation, wortmannin, SB 239063, adiponectin, and thrombin.
Main Results:
- T-cadherin depletion modestly reduced resting transendothelial resistance.
- Depletion altered phosphorylation of Akt, LIM kinase, p38 MAP kinase, and cofilin, and affected tubulin deacetylation.
- T-cadherin depletion influenced the biphasic serum-induced resistance response and reduced sensitivity to thrombin.
Conclusions:
- T-cadherin is implicated in the regulation of endothelial barrier function.
- A complex signaling network links T-cadherin to endothelial barrier regulation, involving pathways like PI3K/Akt and p38 MAP kinase.
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