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

Author:

Bowers Stephanie L. K.12,Davis-Rodriguez Stephanie123,Thomas Zachary M.12,Rudomanova Valeria12,Bacon W. Clark12,Beiersdorfer Alex12,Ma Qing13,Devarajan Prasad13,Blaxall Burns C.12

Affiliation:

1. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio

2. The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

3. Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

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.

Funder

NIH

Publisher

American Physiological Society

Subject

Physiology

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