Adenosine A2A Receptor Occupancy Stimulates Collagen Expression by Hepatic Stellate Cells via Pathways Involving Protein Kinase A, Src, and Extracellular Signal-Regulated Kinases 1/2 Signaling Cascade or p38 Mitogen-Activated Protein Kinase Signaling Pathway

2007 ◽  
Vol 72 (6) ◽  
pp. 1626-1636 ◽  
Author(s):  
Jiantu Che ◽  
Edwin S. L. Chan ◽  
Bruce N. Cronstein
Keyword(s):  
Protein Kinase ◽  
Receptor Occupancy ◽  
Mitogen Activated Protein Kinase ◽  
Collagen Expression ◽  
Extracellular Signal ◽  
A2a Receptor ◽  
Mitogen Activated Protein ◽  
Adenosine A2a ◽  
Protein Kinase Signaling ◽  
Kinase Signaling Pathway

scholarly journals Ras Mutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes

2005 ◽  
Vol 16 (12) ◽  
pp. 5538-5550 ◽  
Author(s):  
James M. Mullin ◽  
James M. Leatherman ◽  
Mary Carmen Valenzano ◽  
Erika Rendon Huerta ◽  
Jon Verrechio ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Mitogen Activated Protein Kinase ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Downstream Effects ◽  
Extracellular Signal ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signaling ◽  
Kinase Signaling Pathway

Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK1 renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of d-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to d-mannitol (Mr 182), polyethylene glycol (Mr 4000), and 10,000-Mr methylated dextran but not to 2,000,000-Mr methylated dextran. This implies a “ceiling” on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier.

Sign in / Sign up

Export Citation Format

Share Document