Lipid peroxidation regulates podocyte migration and cytoskeletal structure through redox sensitive RhoA signaling

Redox Biol. 2018 Jun;16:248-254. doi: 10.1016/j.redox.2018.02.024. Epub 2018 Mar 6.


Early podocyte loss is characteristic of chronic kidney diseases (CKD) in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes. We found that lipid radicals govern changes in podocyte homeostasis through redox sensitive RhoA signaling: lipid radicals inhibit migration and cause loss of F-actin fibers. These effects were prevented by mutating the redox sensitive cysteines of RhoA. We therefore suggest that in diseases associated with increased lipid peroxidation, lipid radicals can determine podocyte function with potentially pathogenic consequences for kidney physiology.

Keywords: Chronic kidney disease; Cysteine; Lipid peroxidation; Podocyte; Reactive lipids; RhoA.

Publication types

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

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Cell Movement / genetics
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • Diabetes Complications / genetics
  • Diabetes Complications / pathology
  • Free Radicals / metabolism
  • Humans
  • Lipid Peroxidation / genetics*
  • Mutation
  • Obesity / complications
  • Obesity / genetics
  • Obesity / pathology
  • Oxidation-Reduction
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / pathology
  • Signal Transduction
  • rhoA GTP-Binding Protein / genetics*


  • Actins
  • Free Radicals
  • rhoA GTP-Binding Protein