Pigment epithelium-derived factor inhibits high glucose-induced JAK/STAT signalling pathway activation in human glomerular mesangial cells

ABSTRACT

To further elucidate the mechanism of the anti-fibrogenic role of pigment epithelium-derived factor [PEDF] on diabetic nephropathy. Human glomerular mesangial cells [HMCs] were treated with 30 mmol/l D-glucose for different time intervals [6, 12, 24, and 48 hrs]. To examine the beneficial effect of PEDF, we incubated the HMCs with high glucose [30 mmol/L] in the presence of different concentrations of PEDF [10, 40, and 100 nmol/l] for 24 hrs. The study took place in the Laboratory of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, China between July 2012 and December 2012. Transforming growth factor-beta1 [TGF-beta1] and fibronectin [FN] mRNA was measured by RT-PCR. The protein synthesis of TGF-beta1 and FN in the culture medium of HMC was detected by enzyme-linked immunosorbent assay. The phosphorylation levels of Janus kinase2 [JAK2] and signal transducers and activators of transcription1 [STAT1] were measured using western blotting. The exposure of HMCs to 30 mmol/L glucose caused the activation of JAK2 and STAT1. It upregulated TGF-beta1 expression and increased protein synthesis of FN. These high glucose-induced changes were suppressed by PEDF. The PEDF can decrease the expression of TGF-beta1 and FN, possibly by inhibiting the phosphorylation of JAK/STAT, which may offer a promising strategy in the treatment of diabetic nephropathy