PMID- 27190325
OWN - NLM
STAT- MEDLINE
DCOM- 20170906
LR  - 20181202
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 31
IP  - 11
DP  - 2016 Nov
TI  - Resveratrol delays polycystic kidney disease progression through attenuation of 
      nuclear factor kappaB-induced inflammation.
PG  - 1826-1834
AB  - 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 kappaB (NF-kappaB) 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-alpha (TNF-alpha) and complement 
      factor B (CFB) in Cy/+ rat kidneys in parallel with the decreased activity of 
      NF-kappaB (p50/p65). The activation of NF-kappaB 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-alpha and CFB and 
      reduced NF-kappaB activity in ADPKD cells. Moreover, NF-kappaB 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-kappaB 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.
CI  - (c) The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. 
      All rights reserved.
FAU - Wu, Ming
AU  - Wu M
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Gu, Junhui
AU  - Gu J
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Mei, Shuqin
AU  - Mei S
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Xu, Dechao
AU  - Xu D
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Jing, Ying
AU  - Jing Y
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Yao, Qing
AU  - Yao Q
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Chen, Meihan
AU  - Chen M
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Yang, Ming
AU  - Yang M
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Chen, Sixiu
AU  - Chen S
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Yang, Bo
AU  - Yang B
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Qi, Na
AU  - Qi N
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Hu, Huimin
AU  - Hu H
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Wuthrich, Rudolf P
AU  - Wuthrich RP
AD  - Division of Nephrology, University Hospital, Zurich, Switzerland.
FAU - Mei, Changlin
AU  - Mei C
AD  - Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20160419
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Stilbenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - Q369O8926L (Resveratrol)
SB  - IM
CIN - Nephrol Dial Transplant. 2016 Nov;31(11):1755-1758. PMID: 27190353
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Case-Control Studies
MH  - Chemokine CCL2/metabolism
MH  - Disease Progression
MH  - Dogs
MH  - Humans
MH  - Inflammation/metabolism/pathology/*prevention & control
MH  - Madin Darby Canine Kidney Cells
MH  - Male
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Polycystic Kidney Diseases/metabolism/pathology/*prevention & control
MH  - Polycystic Kidney, Autosomal Dominant/metabolism/pathology/*prevention & control
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Resveratrol
MH  - Signal Transduction
MH  - Stilbenes/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Zebrafish
OTO - NOTNLM
OT  - NF-kappaB
OT  - autosomal dominant polycystic kidney disease
OT  - inflammation
OT  - mTOR
OT  - macrophages
EDAT- 2016/11/04 06:00
MHDA- 2017/09/07 06:00
CRDT- 2016/05/19 06:00
PHST- 2015/10/29 00:00 [received]
PHST- 2016/02/24 00:00 [accepted]
PHST- 2016/11/04 06:00 [pubmed]
PHST- 2017/09/07 06:00 [medline]
PHST- 2016/05/19 06:00 [entrez]
AID - gfw058 [pii]
AID - 10.1093/ndt/gfw058 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2016 Nov;31(11):1826-1834. doi: 10.1093/ndt/gfw058. Epub 
      2016 Apr 19.