Role of tea polyphenols in delaying hyperglycemia-induced senescence in human glomerular mesangial cells via miR-126/Akt-p53-p21 pathways.

Abstract

The aim of this study was to investigate the effects and possible mechanism of tea polyphenols (TPs) on the senescence of human glomerular mesangial cells (HGMCs) under high glucose conditions. HGMCs were divided into the normal group (NG, 5.5mmol/L glucose), mannitol group (MNT, 5.5mmol/L glucose and 24.5mmol/L mannitol), TP group (TP, 30mmol/L glucose and 5 μg/mL TP) and high-dose D-glucose group (HG, 30mmol/L glucose). The effects of TP on the cell morphology of HGMCs; the percentage of cells positive for senescence-associated β-galactosidase (SA-β-gal); the ratio of G1 phase of cell cycle; telomere length; and the expression of p-Akt, p53, p21 and Rb proteins of the Akt-p53-p21 signaling pathway and the expression miR-126 were examined. High glucose led to premature senescence of HGMCs, as evident from the increase in the percentage of SA-β-gal-positive cells, decrease in telomere length, cell cycle arrest at G1 phase,decrease in the expression of miR-126 and p-Akt and increase in the expression of p53, p21 and Rb proteins in the HG group. In contrast, in the TP group, these effects of high glucose treatment were abrogated and this indicates that TP had a protective effect on HGMCs. High glucose induces the senescence of HGMCs in vitro via the miR-126 and Akt-p53-p21 signaling pathways. TP can delay the high glucose-induced senescence of HGMCs by regulating the activity of these signaling pathways. Thus, the polyphenols present in tea may have potential for the treatment of diabetic nephropathies associated with premature senescence.