Recombinant Long-Acting Thioredoxin Ameliorates AKI to CKD Transition via Modulating Renal Oxidative Stress and Inflammation

Int J Mol Sci. 2021 May 25;22(11):5600. doi: 10.3390/ijms22115600.

Abstract

An effective strategy is highly desirable for preventing acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Thioredoxin-1 (Trx), a redox-active protein that has anti-oxidative and anti-inflammatory properties, would be a candidate for this but its short half-life limits its clinical application. In this study, we examined the renoprotective effect of long-acting Trx that is comprised of human albumin and Trx (HSA-Trx) against AKI to CKD transition. AKI to CKD mice were created by renal ischemia-reperfusion (IR). From day 1 to day 14 after renal IR, the recovery of renal function was accelerated by HSA-Trx administration. On day 14, HSA-Trx reduced renal fibrosis compared with PBS treatment. At the early phase of fibrogenesis (day 7), HSA-Trx treatment suppressed renal oxidative stress, pro-inflammatory cytokine production and macrophage infiltration, thus ameliorating tubular injury and fibrosis. In addition, HSA-Trx treatment inhibited G2/M cell cycle arrest and apoptosis in renal tubular cells. While renal Trx protein levels were decreased after renal IR, the levels were recovered by HSA-Trx treatment. Together, HSA-Trx has potential for use in the treatment of AKI to CKD transition via its effects of modulating oxidative stress and inflammation.

Keywords: acute kidney injury; albumin fusion; chronic kidney disease; thioredoxin.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Apoptosis / drug effects*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology
  • Thioredoxins / administration & dosage*
  • Thioredoxins / pharmacology

Substances

  • Reactive Oxygen Species
  • Thioredoxins