Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor κB-induced inflammation

Nephrol Dial Transplant. 2016 Nov;31(11):1826-1834. doi: 10.1093/ndt/gfw058. Epub 2016 Apr 19.

Abstract

Background: Inflammation plays an important role in polycystic kidney disease (PKD). The current study aimed to examine the efficacy of the anti-inflammatory compound resveratrol in PKD and to investigate its underlying mechanism of action.

Methods: Male Han:SPRD (Cy/+) rats with PKD were treated with 200 mg/kg/day resveratrol or vehicle by gavage for 5 weeks. Human autosomal dominant (AD) PKD cells, three-dimensional (3D) Madin-Darby canine kidney cells and zebrafish were treated with various concentrations of resveratrol or the nuclear factor κB (NF-κB) inhibitor QNZ.

Results: Resveratrol treatment reduced blood urea nitrogen levels and creatinine levels by 20 and 24%, respectively, and decreased two-kidney/total body weight ratio by 15% and cyst volume density by 24% in Cy/+ rats. The proliferation index and the macrophage infiltration index were reduced by 40 and 43%, respectively, in resveratrol-treated cystic kidneys. Resveratrol reduced the levels of the pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and complement factor B (CFB) in Cy/+ rat kidneys in parallel with the decreased activity of NF-κB (p50/p65). The activation of NF-κB and its correlation with pro-inflammatory factor expression were confirmed in human ADPKD cells and kidney tissues. Resveratrol and QNZ inhibited the expression of MCP-1, TNF-α and CFB and reduced NF-κB activity in ADPKD cells. Moreover, NF-κB blockage minimized the inhibition of inflammatory factor production by resveratrol treatment. Furthermore, resveratrol or QNZ inhibited cyst formation in the 3D cyst and zebrafish models.

Conclusions: The NF-κB signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future.

Keywords: NF-κB; autosomal dominant polycystic kidney disease; inflammation; mTOR; macrophages.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Case-Control Studies
  • Chemokine CCL2 / metabolism
  • Disease Progression
  • Dogs
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Madin Darby Canine Kidney Cells
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Polycystic Kidney Diseases / metabolism
  • Polycystic Kidney Diseases / pathology
  • Polycystic Kidney Diseases / prevention & control*
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Polycystic Kidney, Autosomal Dominant / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Signal Transduction
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Zebrafish

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • CCL2 protein, human
  • Chemokine CCL2
  • NF-kappa B
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Resveratrol