C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis

V.A. Rufanova, E. Lianos, A. Alexanian, E. Sorokina, M. Sharma, Ann McGinty, A. Sorokin

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7 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalKidney International
Volume75
Issue number1
Early online date10 Sep 2008
DOIs
Publication statusPublished - Jan 2009

ASJC Scopus subject areas

  • Nephrology

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    Rufanova, V. A., Lianos, E., Alexanian, A., Sorokina, E., Sharma, M., McGinty, A., & Sorokin, A. (2009). C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis. Kidney International, 75(1), 31-40. https://doi.org/10.1038/ki.2008.448