Peroxiredoxin 3 deficiency accelerates chronic kidney injury in mice through interactions between macrophages and tubular epithelial cells.

Chronic kidney disease (CKD) has become epidemic worldwide. Mitochondrial reactive oxygen species (ROS)-induced oxidative stress is an important mediator of CKD, and Prx3 plays a critical role in maintenance of mitochondrial ROS. The present study examined the role of Prx3 in the context of fibrosis, a common feature of CKD, using Prx3 KO mice under obstructive and diabetic stress. Prx3 deficiency accelerated fibrosis and inflammation accompanied by mitochondrial oxidative stress in obstructed and diabetic kidneys as well as in proximal tubular epithelial (mProx) cells. In addition, Prx3 deficiency induced Raw264.7 macrophages activation, leading to upregulation of proinflammatory cytokines. Conditioned media from LPS-stimulated Prx3 deficient macrophages accelerated proinflammatory and profibrotic cytokines in mProx cells. Interestingly, Prx3 deficiency induced most inflammatory and fibrotic cytokines at basal condition in both tissues and cells. Taken together, these results demonstrate that Prx3 deficiency can accelerate CKD through interactions between macrophages and tubular epithelial cells.