Advanced glycation end products-induced apoptosis attenuated by PPARδ activation and epigallocatechin gallate through NF-κB pathway in human embryonic kidney cells and human mesangial cells

Yao Jen Liang, Jhin Hao Jian, Yuan Chun Liu, Shiow Jen Juang, Kou Gi Shyu, Ling Ping Lai, Bao Wei Wang, Jyh Gang Leu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor δ (PPARδ) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). Methods: The HEK cells and HMC were separated into the following groups: 100μg/mL AGE alone for 18 h; AGE treated with 1μM L-165041 or 10μM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-κB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. Results: AGE significantly increased tumour necrosis factor-α (TNF-α), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pretreatment with L-165041 or EGCG. AGE-induced nuclear factor-κB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. Conclusions: This study demonstrated that PPARδ agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARδ agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy.

Original languageEnglish
Pages (from-to)406-416
Number of pages11
JournalDiabetes/Metabolism Research and Reviews
Volume26
Issue number5
DOIs
Publication statusPublished - Jul 2010

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4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid
Peroxisome Proliferator-Activated Receptors
Advanced Glycosylation End Products
Mesangial Cells
Apoptosis
Kidney
Diabetic Nephropathies
Superoxide Dismutase
Cytokines
Inflammation
HEK293 Cells
epigallocatechin gallate
Tumor Necrosis Factor-alpha
Research Personnel
Gene Expression
Messenger RNA
Advanced Glycosylation End Product-Specific Receptor
Therapeutics

Keywords

  • Advanced glycation end products
  • Apoptosis
  • Diabetic nephropathy
  • Epigallocatechin gallate
  • Peroxisome proliferator-activated receptors δ

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Advanced glycation end products-induced apoptosis attenuated by PPARδ activation and epigallocatechin gallate through NF-κB pathway in human embryonic kidney cells and human mesangial cells. / Liang, Yao Jen; Jian, Jhin Hao; Liu, Yuan Chun; Juang, Shiow Jen; Shyu, Kou Gi; Lai, Ling Ping; Wang, Bao Wei; Leu, Jyh Gang.

In: Diabetes/Metabolism Research and Reviews, Vol. 26, No. 5, 07.2010, p. 406-416.

Research output: Contribution to journalArticle

Liang, Yao Jen ; Jian, Jhin Hao ; Liu, Yuan Chun ; Juang, Shiow Jen ; Shyu, Kou Gi ; Lai, Ling Ping ; Wang, Bao Wei ; Leu, Jyh Gang. / Advanced glycation end products-induced apoptosis attenuated by PPARδ activation and epigallocatechin gallate through NF-κB pathway in human embryonic kidney cells and human mesangial cells. In: Diabetes/Metabolism Research and Reviews. 2010 ; Vol. 26, No. 5. pp. 406-416.
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abstract = "Background: Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor δ (PPARδ) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). Methods: The HEK cells and HMC were separated into the following groups: 100μg/mL AGE alone for 18 h; AGE treated with 1μM L-165041 or 10μM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-κB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. Results: AGE significantly increased tumour necrosis factor-α (TNF-α), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pretreatment with L-165041 or EGCG. AGE-induced nuclear factor-κB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. Conclusions: This study demonstrated that PPARδ agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARδ agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy.",
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AU - Jian, Jhin Hao

AU - Liu, Yuan Chun

AU - Juang, Shiow Jen

AU - Shyu, Kou Gi

AU - Lai, Ling Ping

AU - Wang, Bao Wei

AU - Leu, Jyh Gang

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AB - Background: Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor δ (PPARδ) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). Methods: The HEK cells and HMC were separated into the following groups: 100μg/mL AGE alone for 18 h; AGE treated with 1μM L-165041 or 10μM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-κB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. Results: AGE significantly increased tumour necrosis factor-α (TNF-α), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pretreatment with L-165041 or EGCG. AGE-induced nuclear factor-κB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. Conclusions: This study demonstrated that PPARδ agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARδ agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy.

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