Figure 9. Suggested scheme of therapeutic effects of APX-115 on STZ-induced diabetic kidney injury.

We summarize here our overall findings schematically, with a focus on how Noxs-mediated ROS production may be a trigger for increased oxidative metabolism leading to mitochondrial and peroxisomal dysfunction associated with lipid accumulation as well as activation of different signaling pathway leading to increased inflammatory responses and profibrotic factors in DKD. In addition, ROS triggers kidney cells to secret cytokines which potentiate recruitment and activation of macrophages and then, the activated macrophages also contribute to DKD. Interestingly, pan-Nox inhibitor, APX-115 attenuates most of the ROS-mediated effects (shown as green arrows), suggesting that APX-115 may become a new therapeutic strategy against DKD.