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

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

doi:10.1093/ndt/gfw058

Cited by 51 publications

(40 citation statements)

References 35 publications

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“…Based on these data, we hypothesize that IRF5 ASO treatment reduces cystic index by reducing the ability of macrophages to produce cystpromoting cytokines such as TNFa and IL-6 (26). Both of these cytokines, and their associated downstream signaling pathways including p-STAT3, are expressed in renal macrophages (33,34) and have been implicated in progression of cystic disease (35)(36)(37)(38). To test this hypothesis, we flow sorted Figure 3.…”

Section: Suppression Of Irf5 Reduces Macrophage Proinflammatory Cytokmentioning

confidence: 99%

Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease

et al. 2020

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Background Autosomal dominant polycystic kidney disease is caused by genetic mutations in PKD1 or PKD2. Macrophages and their associated inflammatory cytokines promote cyst progression; however, transcription factors within macrophages that control cytokine production and cystic disease are unknown.Methods In these studies, we used conditional Pkd1 mice to test the hypothesis that macrophage-localized interferon regulatory factor-5 (IRF5), a transcription factor associated with production of cyst-promoting cytokines (TNFa, IL-6), is required for accelerated cyst progression in a unilateral nephrectomy (1K) model. Analyses of quantitative real-time PCR (qRT-PCR) and flow-cytometry data 3 weeks post nephrectomy, a time point before the onset of severe cystogenesis, indicate an accumulation of inflammatory infiltrating and resident macrophages in 1K Pkd1 mice compared with controls. qRT-PCR data from FACS cells at this time demonstrate that macrophages from 1K Pkd1 mice have increased expression of Irf5 compared with controls. To determine the importance of macrophage-localized Irf5 in cyst progression, we injected scrambled or IRF5 antisense oligonucleotide (ASO) in 1K Pkd1 mice and analyzed the effect on macrophage numbers, cytokine production, and renal cystogenesis 6 weeks post nephrectomy.Results Analyses of qRT-PCR and IRF5 ASO treatment significantly reduced macrophage numbers, Irf5 expression in resident-but not infiltrating-macrophages, and the severity of cystic disease. In addition, IRF5 ASO treatment in 1K Pkd1 mice reduced Il6 expression in resident macrophages, which was correlated with reduced STAT3 phosphorylation and downstream p-STAT3 target gene expression.Conclusions These data suggest that Irf5 promotes inflammatory cytokine production in resident macrophages resulting in accelerated cystogenesis.

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Section: Suppression Of Irf5 Reduces Macrophage Proinflammatory Cytokmentioning

confidence: 99%

Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease

et al. 2020

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“…Resveratrol (RES) is naturally occurring plant antibiotic known as phytoalexin, found in various plants, nuts, fruits and especially abundant in grapes and red wine1617. It has been extensively studied for its antioxidant, anti-aging and anti-inflammatory activities181920212223. In addition, in vivo and in vitro studies showed that RES possesses potential anti-tumor activity against several malignancies24252627.…”

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confidence: 99%

Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity

Khaleel

Al‐Abd

Ali

et al. 2016

Sci Rep

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Doxorubicin (DOX) has limited efficacy in colorectal cancer due to multi-drug resistance. Resveratrol (RES) and didox (DID) are polyhydroxyphenols with potential chemosensitizing effects. Herein, we assessed the chemomodulatory effects of RES and DID to DOX in colorectal cancer cells. Equitoxic combination of DOX with RES and DID in HCT 116 reduced the IC50 of DOX from 0.96 ± 0.02 μM to 0.52 ± 0.05 μM and 0.4 ± 0.06 μM, respectively. Similarly, combination of DOX with RES and DID in HT-29 decreased the IC50’s of DOX from 0.88 ± 0.03 μM to 0.47 ± 0.02 μM and 0.29 ± 0.04 μM, respectively. The expressions of p53 and Bax genes were markedly elevated in HCT 116 cells after exposure to DOX/DID. In HT-29 cells, the expression of Bcl-XL gene was significantly decreased after exposure to DOX/DID. In addition, combination of DOX with RES significantly increased the expression of Bax gene in HCT 116 cells. RES treatment induced significant S-phase arrest in DOX-treated HCT 116 cells, while DID induced G2/M- and S-phase arrest in HCT 116 and HT-29, respectively. Both RES and DID significantly enhanced the intracellular entrapment of DOX due to blocking the efflux activity of p-glycoprotein pump. In conclusion, RES and DID sensitize colorectal cancer cells to DOX via facilitating apoptosis and enhancing intracellular entrapment of DOX.

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“…Additionally, resveratrol activates the AMP-activated protein kinase (AMPK) signaling pathway, which again is related to the activation of PGC-1α levels and the beneficial effects of resveratrol on mitochondrial function [88,89]. Furthermore, in a recent study, treatment with resveratrol showed promising results for the delay in PKD progression in Han:SRPD:PKD rats by inhibiting inflammation [90]. These preliminary observations will prompt further research in ADPKD patients [85].…”

Section: Mitochondrial Dysfunction In Adpkdmentioning

confidence: 96%

Oxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?

et al. 2018

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Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 or PKD2 genes, is the most common hereditary renal disease. Renal manifestations of ADPKD are gradual cyst development and kidney enlargement ultimately leading to end-stage renal disease. ADPKD also causes extrarenal manifestations, including endothelial dysfunction and hypertension. Both of these complications are linked with reduced nitric oxide levels related to excessive oxidative stress (OS). OS, defined as disturbances in the prooxidant/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen and nitrogen free radicals. Next to endothelial dysfunction and hypertension, there is cumulative evidence that OS occurs in the early stages of ADPKD. In the current review, we aim to summarize the cardiovascular complications and the relevance of OS in ADPKD and, more specifically, in the early stages of the disease. First, we will briefly introduce the link between ADPKD and the early cardiovascular complications including hypertension. Secondly, we will describe the potential role of OS in the early stages of ADPKD and its possible importance beyond the chronic kidney disease (CKD) effect. Finally, we will discuss some pharmacological agents capable of reducing reactive oxygen species and OS, which might represent potential treatment targets for ADPKD.

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

Abstract: 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.

Cited by 51 publications

References 35 publications

Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease

Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease

Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity

Oxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?

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