title: Pigment epithelium-derived factor inhibits high glucose-induced JAK/STAT signalling pathway activation in human glomerular mesangial cells.
abstract: OBJECTIVE
  To further elucidate the mechanism of the anti-fibrogenic role of pigment epithelium-derived factor (PEDF) on diabetic nephropathy.
  
  
  METHODS
  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 reverse transcription-polymerase chain reaction (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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Tuohua
authors: T
authors: Mao
authors: Hongmin
authors: H
authors: Chen
authors: Lian
authors: L
authors: Hong
authors: Jing
authors: J
authors: Li
mesh_terms: D002478:Cells, Cultured; D005136:Eye Proteins / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D050527:Mesangial Cells; D009414:Nerve Growth Factors / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015843:Serpins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D005353:Fibronectins; D005947:Glucose; D053614:Janus Kinase 2; D009414:Nerve Growth Factors; D050794:STAT1 Transcription Factor; D015843:Serpins; D016212:Transforming Growth Factor beta; D000099174:Pigment Epithelium-Derived Factor; C494079:STAT1 protein, human