Project details

or


Lung tissue expression profiling of NO/cyclic GMP-activated RhoGEF17

Keywords:
vascular medicine Gunanine Nucleotide Exchange Factor lung

Researchers:
prof. dr. M. Schmidt
M. Lutz

Type of project:
Pilot project (year 2 or 3)

Nature of the research:
Research project

Fields of study:
pulmonology

Background / introduction
RhoA is a pivotal regulator of smooth muscle cells (SMC) in the vascular and pulmonary system (1,2). Nowadays it is generally accepted that the activation of Rho-specific guanine nucleotide exchange factors (RhoGEFs) is required for the regulation of cellular RhoA activity. Recently, we have identified a new RhoGEF (3) (RhoGEF17/p164-RhoGEF) which is expressed in smooth muscle cells and which is positively regulated by cyclic GMP-dependent kinase (cGK). Until now, nitric oxide/cGMP/cGK is believed to induce relaxation of SMC (4) and cGK-mediated phosphorylation of RhoA has been shown to contribute to SMC relaxation (5). Under certain conditions, however, alterations in the expression of RhoGEF17 might modulate cGMP-induced relaxation (6). Therefore we will analyze the expression of RhoGEF17 in isolated smooth muscle cells and tracheal strips from different sources and under different conditions.
Research question / problem definition
Differential expression of NO/cyclic GMP-induced RhoGEF17 in tissues and cells from lung origin
Workplan
The expression of RhoGEF17 will be analyzed in immortalized human aortic SMCs, primary SMCs and strips from bovine, mouse and guinea pig trachea by quantitative RT-PCR and immunoblot analysis. Moreover, we will study RhoGEF17 expression under culture conditions known to induce phenotypical switching of SMCs and therefore contribute to disorders such as asthma and chronic obstructive pulmonary disease. Such culture conditions have been established based on recent research in the Department of Molecular Pharmacology, Faculty of Pharmacie, University of Groningen. The experimental work will be done in collaboration with the Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg.
References
1. Loirand G, Guilluy C, Pacaud P. Trends Cardiovasc Med. 2006, 16(6):199-204.
2. Loirand G, Guérin P, Pacaud P. Circ Res. 2006 Feb 17;98(3):322-34.
3. Rümenapp U, Freichel-Blomquist A, Wittinghofer B, Jakobs KH, Wieland T. Biochem J. 2002, 366(Pt 3):721-8.
4. Cerra MC, Pellegrino D., Curr Med Chem. 2007;14(5):585-99.
5. Pilz RB, Casteel DE. Circ Res. 2003, 93(11):1034-46.
6. Gao Y, Portugal AD, Negash S, Zhou W, Longo LD, Usha Raj J. Am J Physiol Lung Cell Mol Physiol. 2007, 292(3):L678-84.
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