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Proliferative mechanisms in kidney cells
J Pfeilschifter1, A Huwiler, V A Briner
1Department of Pharmacology, University of Basel, Switzerland.
Abstract:
The activation of the mitogen-activated protein kinase cascade is one of the major signalling pathways by which growth factors transmit their mitogenic messages from the cell membrane to the nucleus. Two major breakthroughs reported in the past months are the cross-communication between the mitogen-activated protein kinase cascade and the cAMP-protein kinase A signal pathway, and the role of alpha- and beta gamma-complexes of heterotrimeric G proteins in activating the mitogen-activated protein kinase pathway. These signalling strategies have now also been demonstrated in renal mesangial cells. Another important step has been the identification of a candidate gene for polycystic kidney disease. Knowledge of the molecular mechanisms of action of growth factors in the kidney will promote greatly our understanding of the aetiology of renal disease.
Insights
Growth factors activate signaling pathways in kidney cells, revealing new insights into polycystic kidney disease. Understanding these molecular mechanisms is key to understanding kidney disease causes.
Area of Science:
- Molecular biology
- Cell signaling
- Nephrology
Background:
- Mitogen-activated protein kinase (MAPK) cascade is a key pathway for growth factor signaling.
- Cross-talk between MAPK and cAMP-protein kinase A (PKA) pathways is crucial.
- Heterotrimeric G proteins play a role in MAPK pathway activation.
Purpose of the Study:
- To investigate the role of MAPK signaling in renal mesangial cells.
- To explore the cross-communication between MAPK and cAMP-PKA pathways in the kidney.
- To identify candidate genes for polycystic kidney disease.
Main Methods:
- Cellular signaling assays in renal mesangial cells.
- Analysis of growth factor-mediated signal transduction.
- Genetic studies for polycystic kidney disease gene identification.
Main Results:
- Demonstrated MAPK and cAMP-PKA pathway cross-talk in renal mesangial cells.
- Identified the role of G protein alpha- and beta gamma-complexes in MAPK activation.
- Identified a candidate gene associated with polycystic kidney disease.
Conclusions:
- Growth factor signaling in the kidney involves complex cross-talk between MAPK and cAMP-PKA pathways.
- Understanding these pathways is vital for deciphering the etiology of renal diseases, including polycystic kidney disease.