Document Detail


Endothelin signaling via guanine exchange factor C3G in renal glomerular mesangial cells.
MedLine Citation:
PMID:  20725139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The guanine nucleotide exchange factor C3G is one of the mediators of endothelin-1 (ET-1) intracellular signaling cascades and is vital for kidney development and homeostasis. The aim of the current study was to analyze the specificity of ET-1-induced signaling via C3G in rat glomerular mesangial cells (GMC) and to investigate the biological significance of C3G during mesangioproliferative glomerulonephritis. In GMC, C3G expression was increased (1) in vivo after induction of the anti-Thy1 model of glomerulonephritis and (2) in cell culture experiments after fetal bovine serum incubation. To examine the consequences of C3G up-regulation, adenovirus-mediated gene transfer of C3G into cultured glomerular cells was done, and the GTP loading of the small G proteins Rap1 and R-Ras was analyzed. Overexpression of C3G in mesangial cells resulted in enhanced activation of Rap1, but failed to affect the GTP-bound status of R-Ras in ET-1-stimulated cells. C3G overexpression led to significant changes in GMC spreading and migration patterns in response to ET-1 stimulation and increased stress fiber formation, which was mimicked by Rap1A overexpression. Together, these findings suggest (1) the existence of regulatory mechanisms resulting in disease-related up-regulation of C3G in GMC and (2) that an increase in the C3G protein level may contribute to the resolution stage of mesangioproliferative glomerulonephritis by reducing GMC sensitivity to ET-1, modulating cellular motility, and actin dynamics.
Authors:
Victoriya A Rufanova; Anna Alexanian; Tammo Ostendorf; Dirk Bokemeyer; Simon Prosser; Bradley Miller; Andrey Sorokin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  88     ISSN:  1205-7541     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  808-16     Citation Subset:  IM    
Affiliation:
Department of Medicine, Division of Nephrology and Kidney Disease Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, Thy-1 / immunology
Cell Movement / drug effects,  genetics
Cell Shape / drug effects,  genetics
Cell Size / drug effects
Cells, Cultured
Disease Models, Animal
Endothelin-1 / pharmacology*
Gene Expression / genetics
Glomerulonephritis, Membranoproliferative / chemically induced,  immunology,  metabolism*
Guanine Nucleotide-Releasing Factor 2 / genetics,  metabolism*
Guanosine Triphosphate / metabolism
Kidney Glomerulus / metabolism
Male
Mesangial Cells / cytology,  drug effects,  metabolism*
Microfilaments / metabolism
Rats
Rats, Wistar
Receptor, Endothelin A / metabolism
Receptor, Endothelin B / metabolism
Serum / physiology
Signal Transduction / physiology*
Transduction, Genetic
Wound Healing / drug effects,  genetics
rap1 GTP-Binding Proteins / genetics,  metabolism
ras Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
DK41684/DK/NIDDK NIH HHS; HL22563/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, Thy-1; 0/Endothelin-1; 0/Guanine Nucleotide-Releasing Factor 2; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 86-01-1/Guanosine Triphosphate; EC 3.6.5.2/rap1 GTP-Binding Proteins; EC 3.6.5.2/ras Proteins

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