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p42/44MAPK regulates baseline permeability and cGMP-induced hyperpermeability in endothelial cells
Shubha Varma1, Jerome W Breslin, Brajesh K Lal
1Program in Vascular Biology, Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103-2714, USA.
Microvascular Research
|February 28, 2002
Summary
The p42/44 mitogen-activated protein kinase (MAPK) pathway regulates endothelial cell permeability. This pathway is crucial for both baseline permeability and cGMP-induced hyperpermeability in human umbilical vein endothelial cells.
Area of Science:
- Vascular Biology
- Cell Signaling
- Endothelial Function
Background:
- Endothelial permeability is critical for regulating macromolecule transport.
- Mitogen-activated protein kinases (MAPK) are key signaling molecules involved in cellular processes.
- Understanding MAPK regulation of endothelial permeability is vital for vascular health.
Purpose of the Study:
- To investigate the role of p42/44MAPK and p38MAPK signaling pathways in endothelial cell permeability.
- To determine if these MAPK pathways regulate macromolecule flux across human umbilical vein endothelial cells (HUVEC).
Main Methods:
- HUVEC monolayers were cultured on fibronectin-coated membranes.
- Permeability was assessed by measuring the flux of fluorescein isothiocyanate-labeled dextran-70.
- Cells were treated with 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP) and specific MAPK inhibitors (AG126 for p42/44MAPK, SB203580 for p38MAPK).
Main Results:
- 8-Br-cGMP significantly increased HUVEC permeability.
- Inhibition of p42/44MAPK with AG126 blocked the 8-Br-cGMP-induced increase in permeability.
- Inhibition of p38MAPK with SB203580 did not affect cGMP-induced hyperpermeability.
- AG126 also reduced baseline endothelial cell permeability.
Conclusions:
- The p42/44MAPK signaling pathway plays a significant role in regulating both baseline and cGMP-induced endothelial cell permeability.
- The p38MAPK pathway is not involved in the cGMP-mediated regulation of endothelial permeability.
- These findings highlight the specific involvement of p42/44MAPK in controlling endothelial barrier function.