Figure 6.

Schematic diagram summarizing results of this study. Circulating suPAR, which is increased in some patients, including a subset of patients with primary or recurrent FSGS, causes outside-in activation of αVβ3 integrins in podocytes. This results in Rac1-dependent activation of Nox2, which results in production of ROS. Those in turn lead to increased surface expression of TRPC6, which can be seen as an increase in cationic currents evoked by mechanical stimuli. The modulation of TRPC6 requires Src activation, which is in a position to cause a variety of effects on other proteins in slit diaphragm domains.