ROS stimulate reorganization of mesangial cell-collagen gels by tyrosine kinase signaling

Reactive oxygen species (ROS) initiate multiple pathological and physiologi cal cellular responses, including tyrosine phosphorylation of proteins. In this study, we investigated the effects of ROS on cell-extracellular matrix interactions utilizing the floating three-dimensional collagen gel assay. Exposure of mesangial cells grown in three-dimensional culture to H2O2, 3-a mino-1,2,4-triazole (a catalase inhibitor), or puromycin is associated with gel reorganization accompanied by tyrosine phosphorylation of multiple pro teins, including focal adhesion kinase (FAK). Neutrophils cocultured with m esangial cells in three-dimensional culture also induce mesangial cell-coll agen gel reorganization and initiate tyrosine phosphorylation of a similar set of proteins. Collectively, these results show that ROS of either endoge nous or exogenous origin can modulate mesangial cell-extracellular matrix i nteractions through initiation of a phosphotyrosine kinase signaling cascad e. Consequently, ROS may play a role as signaling molecules that regulate m esangial cell-extracellular matrix interactions in both physiological and p athological, conditions.