The extracellular matrix modulates H2O2 degradation and redox signaling in endothelial cells

The molecular processes that are crucial for cell function, such as proliferation, migration and survival, are regulated by hydrogen peroxide (H 2 O 2 ). Although environmental cues, such as growth factors, regulate redox signaling, it was still unknown whether the ECM, a component of the cell microenvironment, had a function in this process. Here, we showed that the extracellular matrix (ECM) differently regulated H 2 O 2 consumption by endothelial cells and that this effect was not general for all types of cells. The analysis of biophysical properties of the endothelial cell membrane suggested that this modification in H 2 O 2 consumption rates was not due to altered membrane permeability. Instead, we found that the ECM regulated GPx activity, a known H 2 O 2 scavenger. Finally, we showed that the extent of PTEN oxidation was dependent on the ECM, indicating that the ECM was able to modulate H 2 O 2 -dependent protein oxidation. Thus, our results unraveled a new mechanism by which the ECM regulates endothelial cell function by altering redox balance. These results pinpoint the ECM as an important component of redox-signaling. • The extracellular matrix (ECM) regulates H 2 O 2 consumption by endothelial cells. • Membrane biophysical properties are not affected by the ECM. • The ECM regulates GPx activity and the extent of PTEN oxidation. • We propose that the ECM modulates redox-signaling by controlling H 2 O 2 degradation.