Faculty Collaboration Database

Endothelin signaling via guanine exchange factor C3G in renal glomerular mesangial cells. Can J Physiol Pharmacol 2010 Aug;88(8):808-16

Date

08/21/2010

Pubmed ID

20725139

DOI

10.1139/Y10-056

Scopus ID

2-s2.0-78650210330 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

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.

Author List

Rufanova VA, Alexanian A, Ostendorf T, Bokemeyer D, Prosser S, Miller B, Sorokin A

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Actin Cytoskeleton
Animals
Antibodies, Monoclonal
Cell Movement
Cell Shape
Cell Size
Cells, Cultured
Disease Models, Animal
Endothelin-1
Gene Expression
Glomerulonephritis, Membranoproliferative
Guanine Nucleotide-Releasing Factor 2
Guanosine Triphosphate
Kidney Glomerulus
Male
Mesangial Cells
Rats
Rats, Wistar
Receptor, Endothelin A
Receptor, Endothelin B
Serum
Signal Transduction
Thy-1 Antigens
Transduction, Genetic
Wound Healing
rap1 GTP-Binding Proteins
ras Proteins