Pigment epithelium-derived factor inhibits high glucose induced oxidative stress and fibrosis of cultured human glomerular mesangial cells.

OBJECTIVES: To evaluate whether pigment epithelium-derived factor (PEDF) could prevent human mesangial cells (HMCs) from elevated glucose-induced oxidative stress and fibrosis.

METHODS: The study took place in the Endocrinology Laboratory of Renmin Hospital of Wuhan University, Wuhan, China from December 2009 to June 2010. The HMCs were treated with different concentrations of dextroglucose (5.6, 15, and 30 mmol/l), and 5.6 mmol/l D-glucose+24.4 mmol/l D-mannitol (osmotic control) for 24 and 48 hours. To examine the beneficial effect of PEDF, HMCs were also incubated with high glucose (30 mmol/L) in the presence of different concentrations of PEDF (5, 10, 40, 100, and 160 nmol/l) for 48 hours.

RESULTS: The PEDF significantly inhibited the overexpression of transforming growth factor-beta 1, and extracellular matrix proteins (fibronectin and collagen IV) induced by the elevated glucose in HMCs. The PEDF also impeded high glucose-induced reactive oxygen species generation in HMCs.

CONCLUSIONS: These results suggest that PEDF by virtue of its anti-oxidative and anti-fibrogenic properties may have a therapeutic potential in diabetic nephropathy.