Epigallocatechin-3-gallate reduces tubular cell apoptosis in mice with ureteral obstruction

Wang, Yanqiu; Liu, Na; Bian, Xue; Sun, Guangping; Du, Feng; Wang, Bowen; Su, Xuesong

doi:10.1016/j.jss.2015.03.034

Cited by 10 publications

(15 citation statements)

References 44 publications

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“…Supplementation with EGCG suppressed expression of the apoptotic protein Bax and active caspase 3, but maintained expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2) in the diabetic kidney (22). Similar findings were observed in models of renal ischemia-reperfusion injury in rats (23) and unilateral ureteral obstruction (UUO) in mice (24).…”

Section: Preclinical Evidence For Molecular Mechanisms Of Egcg In Ckdsupporting

confidence: 79%

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Molecular Mechanisms of Epigallocatechin-3-Gallate for Prevention of Chronic Kidney Disease and Renal Fibrosis: Preclinical Evidence

Kanlaya

Thongboonkerd

2019

Current Developments in Nutrition

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Chronic kidney disease (CKD) is a common public health problem worldwide characterized by gradual decline of renal function over months/years accompanied by renal fibrosis and failure in tissue wound healing after sustained injury. Patients with CKD frequently present with profound signs/symptoms that require medical treatment, mostly culminating in hemodialysis and renal transplantation. To prevent CKD more efficiently, there is an urgent need for better understanding of the pathogenic mechanisms and molecular pathways of the disease pathogenesis and progression, and for developing novel therapeutic targets. Recently, several lines of evidence have shown that epigallocatechin-3-gallate (EGCG), an abundant phytochemical polyphenol derived from Camellia sinensis, might be a promising bioactive compound for prevention of CKD development/progression. This review summarizes current knowledge of molecular mechanisms underlying renoprotective roles of EGCG in CKD based on available preclinical evidence (from both in vitro and in vivo animal studies), particularly its antioxidant property through preservation of mitochondrial function and activation of Nrf2 (nuclear factor erythroid 2-related factor 2)/HO-1 (heme oxygenase-1) signaling, anti-inflammatory activity, and protective effect against epithelial mesenchymal transition. Finally, future perspectives, challenges, and concerns regarding its clinical use in CKD and renal fibrosis are discussed.

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Section: Preclinical Evidence For Molecular Mechanisms Of Egcg In Ckdsupporting

confidence: 79%

“…Additionally, an antiapoptotic effect of EGCG has been demonstrated in UUO mice (24). Decreased expression levels of Bax, active caspase 3, and poly ADP-ribose polymerase were observed in the EGCG-treated mice, indicating inhibition of the apoptotic pathway (24).…”

Section: Preclinical Evidence For Molecular Mechanisms Of Egcg In Ckdmentioning

confidence: 99%

Molecular Mechanisms of Epigallocatechin-3-Gallate for Prevention of Chronic Kidney Disease and Renal Fibrosis: Preclinical Evidence

Kanlaya

Thongboonkerd

2019

Current Developments in Nutrition

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“…Hematoxylin and Eosin or Periodic acid–Schiff stained renal sections ( Fig 1A and 1B ) were evaluated by two independent experienced renal pathologists in a blinded manner. Assessment of renal injury was based on the degree of interstitial infiltration, cortical thickening, tubular dilatation and proximal tubule brush border integrity at day 3 on a scale of increasing damage from 0–5 based on previously published studies[ 11 , 19 – 21 ] ( Fig 1C ). Obstructed kidneys of Sphk2 -/- mice exhibited less structural alteration when compared to WT mice as evidenced by reduced tubular dilation, epithelial cell sloughing and basement membrane thickening.…”

Section: Resultsmentioning

confidence: 99%

Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction

et al. 2018

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Sphingosine Kinase-2 (Sphk2) is responsible for the production of the bioactive lipid Sphingosine-1 Phosphate, a key regulator of tissue repair. Here we address the in vivo significance of Sphingosine Kinase -2 in renal inflammation/fibrosis in response to unilateral ureteral obstruction using both genetic and pharmacological strategies. Obstructed kidneys of Sphk2-/- mice showed reduced renal damage and diminished levels of the renal injury markers TGFβ1 and αSMA when compared to wild type controls. We found a consistently significant increase in anti-inflammatory (M2) macrophages in obstructed Sphk2-/- kidneys by flow cytometry and a decrease in mRNA levels of the inflammatory cytokines, MCP1, TNFα, CXCL1 and ILβ1, suggesting an anti-inflammatory bias in the absence of Sphk2. Indeed, metabolic profiling showed that the pro-inflammatory glycolytic pathway is largely inactive in Sphk2-/- bone marrow-derived macrophages. Furthermore, treatment with the M2-promoting cytokines IL-4 or IL-13 demonstrated that macrophages lacking Sphk2 polarized more efficiently to the M2 phenotype than wild type cells. Bone marrow transplant studies indicated that expression of Sphk2-/- on either the hematopoietic or parenchymal cells did not fully rescue the pro-healing phenotype, confirming that both infiltrating M2-macrophages and the kidney microenvironment contribute to the damaging Sphk2 effects. Importantly, obstructed kidneys from mice treated with an Sphk2 inhibitor recapitulated findings in the genetic model. These results demonstrate that reducing Sphk2 activity by genetic or pharmacological manipulation markedly decreases inflammatory and fibrotic responses to obstruction, resulting in diminished renal injury and supporting Sphk2 as a novel driver of the pro-inflammatory macrophage phenotype.

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“…Studies have demonstrated that catechins exhibit therapeutic effects in immune nephritis (C-BSA nephritis and Masugi nephritis), diabetic nephropathy, renal dysfunction, chronic renal failure, and antibiotic-and heavy metal-induced acute kidney disease (12)(13)(14)(15)(16). Catechins are efficient scavengers of ROS, and enhance the activity and complexation of antioxidant enzymes (17,18).…”

Section: Discussionmentioning

confidence: 99%

Impact of epigallocatechin‑3‑gallate on expression of nuclear factor erythroid 2‑related factor 2 and γ‑glutamyl cysteine synthetase genes in oxidative stress‑induced mouse renal tubular epithelial cells

Sun

et al. 2018

Mol Med Report

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The aim of the present study was to investigate the antioxidant response mechanism of epigallocatechin‑3‑gallate (EGCG) in H2O2‑induced mouse renal tubular epithelial cells (MRTECs). The cultured MRTECs were divided into normal, H2O2 (control) and EGCG treatment groups. The MTT assay was used to assess cell viability, and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), immunocytochemical and western blot analyses were performed to detect the expression of nuclear factor erythroid 2‑related factor 2 (Nrf2) and γ‑glutamyl cysteine synthetase (γ‑GCS). EGCG was able to mitigate H2O2‑mediated cell damage. The RT‑qPCR results demonstrated that EGCG was able to upregulate the gene expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. The immunocytochemistry and western blot analyses demonstrated that EGCG was able to increase the protein expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. Oxidative stress may lead to a decrease in the viability of MRTECs, while EGCG was able to promote the expression of Nrf2 and γ‑GCS in MRTECs, thereby improving the antioxidant capacity of the cells and promoting the repair of oxidative stress injury.

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Epigallocatechin-3-gallate reduces tubular cell apoptosis in mice with ureteral obstruction

Cited by 10 publications

References 44 publications

Molecular Mechanisms of Epigallocatechin-3-Gallate for Prevention of Chronic Kidney Disease and Renal Fibrosis: Preclinical Evidence

Molecular Mechanisms of Epigallocatechin-3-Gallate for Prevention of Chronic Kidney Disease and Renal Fibrosis: Preclinical Evidence

Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction

Impact of epigallocatechin‑3‑gallate on expression of nuclear factor erythroid 2‑related factor 2 and γ‑glutamyl cysteine synthetase genes in oxidative stress‑induced mouse renal tubular epithelial cells

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