title: C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis.
abstract: The guanine nucleotide exchange factor C3G, along with the CrkII adaptor protein, mediates GTP activation of the small GTPase proteins Rap1 and R-Ras, facilitating their activation of downstream signaling pathways, which had been found to be important in the pathogenesis of glomerulonephritis. We found that expression of C3G protein was upregulated in glomerular epithelial cells in an experimental model of accelerated anti-GBM antibody-induced glomerulonephritis expression. To determine the consequence of its increased expression, we transfected C3G (using adenoviral constructs) into cultured glomerular epithelial cells and measured the activated forms (i.e., GTP-bound) forms of Rap1 and R-Ras. Activation of Rap1 was not affected by C3G; however, the basal level of GTP-bound R-Ras was decreased. Further, C3G over-expression enhanced the activation of R-Ras in response to endothelin. Overexpression of C3G also led to a significant reduction in glomerular epithelial cell spreading and decreased the cells' E-cadherin expression and augmented their migration. We found that C3G was overexpressed in accelerated anti-GBM antibody-induced glomerulonephritis and suggest that this modulates glomerular epithelial cell morphology and behavior.
authors.affiliation: Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Victoriya A
authors.initials: VA
authors.lastname: Rufanova
authors.forename: Elias
authors.initials: E
authors.lastname: Lianos
authors.forename: Anna
authors.initials: A
authors.lastname: Alexanian
authors.forename: Elena
authors.initials: E
authors.lastname: Sorokina
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.forename: Ann
authors.initials: A
authors.lastname: McGinty
authors.forename: Andrey
authors.initials: A
authors.lastname: Sorokin
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects*; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism*; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000235:genetics*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001323:Autoantibodies; D015820:Cadherins; D020735:Guanine Nucleotide-Releasing Factor 2; C051951:antiglomerular basement membrane antibody
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