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

• Published in: Nephrology, dialysis, transplantation Vol. 31; no. 11; pp. 1826 - 1834
• Main Authors: Wu, Ming, Gu, Junhui, Mei, Shuqin, Xu, Dechao, Jing, Ying, Yao, Qing, Chen, Meihan, Yang, Ming, Chen, Sixiu, Yang, Bo, Qi, Na, Hu, Huimin, Wüthrich, Rudolf P, Mei, Changlin
• Format: Journal Article
• Language: English
• Published: England 01.11.2016
• Subjects: 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; Signal Transduction; Stilbenes - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Zebrafish; mTOR; NF-κB; macrophages; autosomal dominant polycystic kidney disease; inflammation
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfw058

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.