Reactive oxygen species stimulate reorganization of mesangial cell -collagen gels by inducing tyrosine kinase signaling. Zent, Roy, Menachem Ailenberg, Gregory P. Downey, Melvin Silverman. Membrane Biology Group and Division of Respiratory Medicine*, Department of Medicine, University of Toronto, Ontario, M5S 1A8, Canada
APStracts 5:0195F, 1998.
Reactive oxygen species (ROS) initiate multiple pathological and physiological cellular responses including tyrosine phosphorylation of proteins. In this study we investigate the effects of ROS on cell -extracellular matrix interactions utilizing the floating 3 -dimensional collagen gel assay. Exposure of mesangial cells grown in 3-dimensional culture to hydrogen peroxide (H2O2), aminotriazole (a catalase inhibitor) or puromycin is associated with gel reorganization that is accompanied by tyrosine phosphorylation of multiple proteins including focal adhesion kinase (FAK). Neutrophils co-cultured with mesangial cells in 3-dimensional culture also induce mesangial cell-collagen gel reorganization and initiate tyrosine phosphorylation of a similar set of proteins. Collectively these results show that ROS of either endogenous or exogenous origin can modulate mesangial cell-extracellular matrix interactions through initiation of a phosphotyrosine kinase signaling cascade. Consequently ROS may play a role as signaling molecules that regulate mesangial cell-extracellular matrix interactions in both physiologic and pathological conditions.

Received 27 April 1998; accepted in final form 22 October 1998
APS Manuscript Number F094-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998