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.

CONCLUSION:

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: Tuohua Mao, Hongmin Chen, Lian Hong, Jing Li
• Journal: Saudi medical journal (Saudi Med J) Vol. 34 Issue 8 Pg. 793-800 (Aug 2013) ISSN: 0379-5284 [Print] Saudi Arabia
• PMID: 23974449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Eye Proteins
• Fibronectins
• Nerve Growth Factors
• STAT1 Transcription Factor
• STAT1 protein, human
• Serpins
• Transforming Growth Factor beta
• pigment epithelium-derived factor
• Janus Kinase 2
• Glucose

Topics

• Cells, Cultured
• Eye Proteins (pharmacology)
• Fibronectins (metabolism)
• Glucose (pharmacology)
• Humans
• Janus Kinase 2 (metabolism)
• Mesangial Cells
• Nerve Growth Factors (pharmacology)
• STAT1 Transcription Factor (metabolism)
• Serpins (pharmacology)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (metabolism)