Chemically Modified Heparin Inhibits Mesangial Cell Proliferation Induced by High Glucose through Interfering with the Cell Cycle

Abstract

The aims of this study were to investigate whether chemically modified non-anticoagulation heparin derivate (Periodate-Oxidized/Borohydride-Reduced modified heparin (OR-heparin)) can inhibit high glucose-induced human mesangial cell proliferation and its influence on the cell cycle. OR-heparin with low anticoagulation activity inhibited high glucose-induced early proliferation in a dose-dependent manner. OR-heparin released high glucose-arrested mesangial cells at G₁ phase, and dose-dependently increased S phase. OR-heparin also inhibited high glucose-activated ERK1/2 phosphorylation, induced p27^Kip1 expression, and suppressed reactive oxygen species (ROS) accumulation in a dose-dependent manner. Our results suggest that OR-heparin releases high glucose-arrested cells on G₁ phase and inhibits high glucose-induced mesangial cell proliferation through blocking ERK1/2 phosphorylation and delaying S phase progression, which may be in correlation with OR-heparin suppressing ROS accumulation.