The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α

Abstract

Significant efforts have been made to ameliorate diabetic nephropathy (DN) by inhibiting protein kinase C. However, these efforts have not been successful in human trials, suggesting that novel therapeutic strategies are required. Thus far, it has been reported that green tea polyphenol epigallocatechin gallate (EGCg) improved albuminuria in DN in a human trial. Our previous study revealed that activation of diacylglycerol kinase α (DGKα) plays a crucial role in the amelioration of DN and that EGCg activates DGKα. Here, we investigated whether and how DGKα contributes to the amelioration of DN upon stimulation by EGCg by using streptozotocin-induced type 1 diabetic model mice. Our results revealed that EGCg ameliorated albuminuria in DN through DGKα in vivo, and methylated EGCg, which has higher absorption in the plasma improved albuminuria in DN effectively. Additionally, we showed that c-Src mediated EGCg-induced DGKα translocation and colocalized with the 67 kDa laminin receptor, which is an EGCg receptor. Furthermore, EGCg attenuated the loss of podocytes in DN by preventing a decrease in focal adhesion under high glucose conditions. Our results indicate that the DGKα pathway is an attractive therapeutic target and that activating this pathway is a novel strategy for treating DN.

Green and white teas as health-promoting foods

“…Some studies describe that green tea consumption can reduce the incidence of colorectal cancer tumors. 55,57 The data supports anti-tumour activity due to histone modification, micro-RNA and DNA methylation. 57 On the other hand, at optimum doses (1000 mg/ml every 24h) and under in vitro conditions, it was observed that an aqueous extract of white tea played an important role against the HCT-116 cell line of colon cancer and in the regulation of the tumour suppressor gene pathway.…”

“…Anti-cancer effects of tea have been the focus of much research in recent years. 31,[55][56][57][58][59][60][61][62][63][64][65] Polyphenols in tea play an important role in the prevention and control of cancer progression due to their different properties. 55,56 The mechanisms studied are generally based on antioxidant activity, regulation of the cell cycle, modulation of the immune system and epigenetic control.…”

“…31,[55][56][57][58][59][60][61][62][63][64][65] Polyphenols in tea play an important role in the prevention and control of cancer progression due to their different properties. 55,56 The mechanisms studied are generally based on antioxidant activity, regulation of the cell cycle, modulation of the immune system and epigenetic control. 57,60,63 In general, tea polyphenols suppress tumour growth and cancer cell proliferation, 55,56 while also possess proapoptotic 31,55 and chemopreventive effects.…”

“…55,56 The mechanisms studied are generally based on antioxidant activity, regulation of the cell cycle, modulation of the immune system and epigenetic control. 57,60,63 In general, tea polyphenols suppress tumour growth and cancer cell proliferation, 55,56 while also possess proapoptotic 31,55 and chemopreventive effects. 56 According to in vitro studies, several mechanisms for the anti-cancer effects of tea catechins have been observed.…”

“…31 For the other types of cancer, contradictory findings have been observed. 31 Current research focuses mainly on the effects of tea on colorectal cancer, [55][56][57] breast cancer 61,62,64 and prostate cancer. [58][59][60] Colon cancer begins in the large intestine.…”