title: Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor κB-induced inflammation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Gu
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Mei
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dechao
authors.initials: D
authors.lastname: Xu
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Meihan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Sixiu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qi
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Division of Nephrology, University Hospital, Zürich, Switzerland.
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.affiliation: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism; D018450:Disease Progression; D004285:Dogs; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007690:Polycystic Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015027:Zebrafish
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016328:NF-kappa B; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000077185:Resveratrol
keywords: NF-κB; autosomal dominant polycystic kidney disease; inflammation; mTOR; macrophages