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

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.