Biol. Pharm. Bull. 30(12) 2274—2278 (2007)

subsequent development of mesangial matrix expansion are prominent features of glomerular disease. Diabetic nephropathy is also characterized by early mesangial cell proliferation, followed by accumulation of extracelluar matrix proteins. Cell proliferation is ultimately a nuclear event and is divided into different phases in what is called the cell cycle. Proliferation, hypertrophy, and apoptosis of renal injury are linked at the level of the cell cycle. In vivo, high glucose induces a limited proliferation and hypertrophy, and cell cycle analysis revealed that glucose arrests cells in the G1 phase. 7) Heparin is a polysulfated glycoaminoglycan that has been used as an anticoagulant for 60 years. In addition to its anticoagulant activity, heparin has numerous biological activities such as anti-inflammatory and anti-metastatic activities. These activities are associated with the complicated structure of heparin. Heparin comprises alternating repeating disaccharide units of varying lengths with an amino sugar (either glucosamine or galactosamine) and uronic acid (either glucuronic or iduronic acid) residue. Heparin has been used for the treatment of glomerulonephritis in several experimental and human glomerular diseases including diabetic nephropathy. Heparin can suppress the matrix expression of mesangial cells induced by high glucose in vitro. However, its strong anticoagulant activity and potentiality of bleeding contraindicates its usage in this field. Many investigators have therefore undertaken to try to find heparin derivatives with low anticoagulant activity but preserving its ability for the treatment of glomerular diseases. It has been reported that some heparin derivatives (low molecular-weight heparin, N-desulfated/acetylated heparin, sulodexide (low molecular-weight heparin and dermatan sulphate mixture) have beneficial effects on nephropathy. Diabetic nephropathy is the leading cause of endstage renal disease, and is characterized by early proliferation and hypertrophy. Exposing murine mesangial cells to high glucose has a biphasic effect on growth, being pro-proliferation early at 24 h of incubation, but antiproliferative thereafter, leading to G1 arrest. G1 phase arrest is associated with cell hypertrophy. A biphasic growth response of early proliferation and subsequent hypertrophy in mesangial cells was also observed in vivo in streptozotocin-induced diabetes mellitus. Therefore, cell cycle alteration is intimately associated with diabetic nephropathy and cell cycle regulation may be used for development of future therapeutics. Antioxidants, taurine and vitamin E, reversed the antiproliferative effect of high glucose in cultured mesangial cells. Previous study has indicated that heparin does not have direct antioxidant activity. Whether chemically modified heparin has ability to inhibit high glucose-induced mesangial cell growth and its possible mechanism are still unknown. A major point of concern in the long-term treatment of diabetic nephropathy with heparin is the risk of bleeding. OR-heparin, a non-anticoagulation heparin derivate, provides a unique opportunity for treatment of diabetic nephropathy. In the present study, we investigated whether OR-heparin can inhibit mesangial cell proliferation induced by high glucose, and its influence on the cell cycle.