Peroxidasin and Eosinophil Peroxidase, but not Myeloperoxidase, Contribute to Renal Fibrosis in the Murine Unilateral Ureteral Obstruction Model.

Peroxidasin and Eosinophil Peroxidase, but not Myeloperoxidase, Contribute to Renal Fibrosis in the Murine Unilateral Ureteral Obstruction Model.
Am J Physiol Renal Physiol. 2018 Dec 19;:
Authors: Colon S, Luan H, Liu Y, Meyer C, Gewin L, Bhave G
Abstract
Renal fibrosis is the pathologic hallmark of chronic kidney disease (CKD) and manifests as glomerulosclerosis and tubulointerstitial fibrosis. Reactive oxygen species (ROS) contribute significantly to renal inflammation and fibrosis, but most research has focused on superoxide (O2.-) and hydrogen peroxide (H2O2). The animal heme peroxidases myeloperoxidase (MPO), eosinophil peroxidase (EPX), and peroxidasin (PXDN), uniquely metabolize H2O2 into highly reactive and destructive hypohalous acids, such as hypobromous (HOBr) and hypochlorous (HOCl) acid. But the role of these peroxidases and their downstream hypohalous acids in the pathogenesis of renal fibrosis is unclear. Our study defines the contribution of MPO, EPX, and PXDN to renal inflammation and tubulointerstitial fibrosis in the murine unilateral ureteral obstruction (UUO) model. Using a non-specific inhibitor of animal heme peroxidases and peroxidase specific knock-out mice, we find that loss of EPX or PXDN, but not MPO, reduces renal fibrosis. Furthermore, we demonstrate that eosinophils, the source of EPX, accumulate in the renal interstitium after UUO. These findings point to EPX and PXDN as potential therapeutic targets f...

Source: American Journal of Physiology. Renal Physiology - December 19, 2018 Category: Physiology Authors: Colon S, Luan H, Liu Y, Meyer C, Gewin L, Bhave G Tags: Am J Physiol Renal Physiol Source Type: research