Inhibition of fibronectin polymerization alleviates kidney injury due to ischemia-reperfusion

Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1293-F1298. doi: 10.1152/ajprenal.00117.2019. Epub 2019 Apr 24.

Abstract

Fibrosis is a common feature of chronic kidney disease; however, no clinical therapies effectively target the progression of fibrosis. Inhibition of fibronectin polymerization with the small peptide pUR4 attenuates fibrosis in the liver and heart. Here, we show that pUR4 decreases renal fibrosis and tissue remodeling using a clinically relevant model of kidney injury, unilateral ischemia-reperfusion. This work highlights the benefits of inhibiting matrix polymerization, alone or in conjunction with cell-based therapies, as a novel approach to diminish the maladaptive responses to ischemic kidney injury that lead to chronic renal failure.

Keywords: acute kidney injury; chronic kidney disease; fibronectin; fibrosis; ischemia-reperfusion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Disease Models, Animal
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Fibronectins / metabolism*
  • Fibrosis
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice, Inbred C57BL
  • Peptide Fragments / pharmacology*
  • Polymerization
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • Fibronectins
  • Peptide Fragments
  • pUR4 peptide