Chemically modified heparin inhibits mesangial cell proliferation induced by high glucose through interfering with the cell cycle.
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 G(1) 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 G(1) 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.
Yin
Deng-Ke
DK
School of Life Science and Technology, China Pharmaceutical University, 24 Tongjia Road, Nanjing City 210009, China.
Yao
Wen-Bing
WB
Gao
Xiang-Dong
XD
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D010314:Partial Thromboplastin Time; D010766:Phosphorylation; D017382:Reactive Oxygen Species
D000925:Anticoagulants; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006493:Heparin; D051357:Cyclin-Dependent Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose