Exogenous pentraxin-3 inhibits the reactive oxygen species-mitochondrial and apoptosis pathway in acute kidney injury

PLoS One. 2018 Apr 19;13(4):e0195758. doi: 10.1371/journal.pone.0195758. eCollection 2018.

Abstract

Pentraxin-3 (PTX3) is a long-form member of the pentraxin family of proteins that has been studied in inflammatory diseases and in various organs. We found that PTX3 protects kidney cells during ischemia and proinflammatory acute kidney injury. The aim of this study was to develop an in vitro experimental model of acute kidney injury and to analyze the protective mechanism of exogenous recombinant PTX3. In this study, cells of the HK-2 renal tubular cell line were treated with a calcium ionophore (A23187), which induced injury by increasing intracellular calcium concentrations and inducing calpain activity and the generation of reactive oxygen species. Exposure of cells to PTX3 significantly attenuated these effects. In addition, the activity of caspase-3 and PARP-1 were decreased in ischemic cells exposed to exogenous recombinant PTX3. PTX3 stabilized the mitochondrial membrane potential and suppressed apoptosis, resulting in the protection of renal tubular cells from ischemic injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Apoptosis / drug effects
  • C-Reactive Protein / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Hypoxia / drug therapy
  • Hypoxia / metabolism
  • Ischemia / drug therapy
  • Ischemia / metabolism
  • Matrix Metalloproteinases
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Protective Agents / pharmacology
  • Reactive Oxygen Species / metabolism*
  • Serum Amyloid P-Component / pharmacology*

Substances

  • Protective Agents
  • Reactive Oxygen Species
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Matrix Metalloproteinases

Grants and funding

We acknowledge funding by the "Dongwha Holdings" Faculty Research Assistance Program of Yonsei University College of Medicine with the grant agreement 6-2015-0064 to WKH. The funders had the decision to publish the manuscript.