Peroxidasin and eosinophil peroxidase, but not myeloperoxidase, contribute to renal fibrosis in the murine unilateral ureteral obstruction model

Selene Colon, Haiyan Luan, Yan Liu, Cameron Meyer, Leslie Gewin, Gautam Bhave

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Renal fibro-sis is the pathological hallmark of chronic kidney disease (CKD) and manifests as glomerulosclerosis and tubulointerstitial fibrosis. Reactive oxygen species contribute significantly to renal inflammation and fibrosis, but most research has focused on superoxide 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 and hypochlorous acid. However, 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 nonspecific inhibitor of animal heme peroxidases and peroxidase-specific knockout 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 for renal fibrosis and CKD and suggest that eosinophils modulate the response to renal injury.

Original languageEnglish
Pages (from-to)F360-F371
JournalAmerican Journal of Physiology - Renal Physiology
Volume316
Issue number2
DOIs
StatePublished - 2019

Keywords

  • Eosinophil peroxidase
  • Hypohalous acid
  • Myeloperoxidase
  • Peroxidasin
  • Reactive oxygen species
  • Renal fibrosis
  • Unilateral ureteral obstruction

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