Effects of Epigallocatechin-3-Gallate on the Expression of TGF-β1, PKC α/βII, and NF-κB in High-Glucose-Stimulated Glomerular Epithelial Cells

Abstract

Epigallocatechin-3-gallate (EGCG) is the most potent antioxidant polyphenol in green tea. In the present study, we investigated whether EGCG plays a role in the expression of transforming growth factor-beta1 (TGF-β1), protein kinase C (PKC) α/βII, and nuclear factor-kappaB (NF-κB) in glomerular epithelial cells (GECs) against high-glucose injury. Treatment with high glucose (30 mM) increased reactive oxygen species (ROS)/lipid peroxidation (LPO) and decreased glutathione (GSH) in GECs. Pretreatment with 100 µM EGCG attenuated the increase in ROS/LPO and restored the levels of GSH, whereas ROS, LPO, and GSH levels were not affected by treatment with 30 mM mannitol as an osmotic control. Interestingly, high-glucose treatment affected 3 separate signal transduction pathways in GECs. It increased the expression of TGF-β1, PKC α/βII, and NF-κB in GECs, respectively. EGCG (1, 10, 100 µM) pretreatment significantly decreased the expression of TGF-β1 induced by high glucose in a dose-dependent manner. In addition, EGCG (100 µM) inhibited the phosphorylation of PKC α/βII caused by glucose at 30 mM. Moreover, EGCG (1, 10, 100 µM) pretreatment significantly decreased the transcriptional activity of NF-κB induced by high glucose in a dose-dependent manner. These data suggest that EGCG could be a useful factor in modulating the injury to GECs caused by high glucose.

Polyphenol compounds and PKC signaling

“…The neuroprotective mechanism of EGCG against oxidative stress-induced cell death includes stimulation of PKC and modulation of cell survival/cell cycle genes [151]. Besides, EGCG (100 μM) down-regulated glucose-induced phosphorylation of PKCα and PKCβII in glomerular epithelial cells thereby providing nephroprotection [152]. EGCG's promotion of keratinocyte differentiation at 5–40 μM was found to be PKCδ-dependent, but neither PKCα nor PKCε-dependent [153].…”

Impact of EGCG Supplementation on the Progression of Diabetic Nephropathy in Rats: An Insight into Fibrosis and Apoptosis

“…Therefore, any phytochemical that addresses glycemic control and podocyte loss by preventing apoptosis and regulates TGF-β levels will be a promising therapeutic agent that targets diabetic nephropathy. EGCG (epigallocatechin-3-gallate) is shown to possess an antihyperglycemic effect , and an antifibrotic effect, , and also has a protective effect against ROS production in diabetic nephropathy induced mouse kidneys . Therefore, we intended to investigate the role of EGCG in ameliorating apoptosis in the kidneys of rats induced with diabetic nephropathy.…”

Epigallocatechin-3-Gallate Attenuates Unilateral Ureteral Obstruction-Induced Renal Interstitial Fibrosis in Mice

“…EGCG can also ameliorate glucose toxicity and renal injury in streptozotocin-induced diabetic rats (Yamabe et al 2006). EGCG also mitigates experimental fibrosis in various organs, including the liver (Safer et al 2012;Xiao et al 2014), heart (Cai et al 2013;Shen et al 2012) and lungs (Sriram et al 2008;You et al 2014), and some studies have indicated that EGCG regulates TGF-β signaling (Park et al 2011;Xiao et al 2014). However, the protective effect of EGCG against renal interstitial fibrosis has not been studied to date.…”